subject:(Prions)

1. Hoover, Clare Elizabeth. Biologic and biochemical features of prion pathogenesis.

Degree: PhD, Microbiology, Immunology, and Pathology, 2016, Colorado State University

► Prions are the causative agents of a group of fatal neurodegenerative diseases known as transmissible spongiform encephalopathies. Prions are unique in that disease is initiated… (more)

▼ Prions are the causative agents of a group of fatal neurodegenerative diseases known as transmissible spongiform encephalopathies. Prions are unique in that disease is initiated when the normal prion protein (PrPC) undergoes a conformational change and propagates through a process of templated conversion to an infectious, misfolded, isoform (PrPRES, PrPCWD, or PrPSc) which can assemble into oligomers and amyloid fibrils. Disease is associated with prion accumulation in the central nervous system, causing the pathologic lesions of neurodegeneration, white matter spongiosis, and a reactive astrogliosis. Previous work has demonstrated the process of prion propagation and disease pathogenesis can be influenced by conversion cofactors, inhibitors, and biologic systems. Heat shock proteins have been shown to protect against the toxic disease effects of denatured and aggregated proteins in several models of neurodegenerative diseases including Alzheimer’s disease, Parkinson’s disease, and spinocerebellar ataxia. In this dissertation, I investigated if heat shock protein 72 (HSP72) expression in neurons could protect against prion disease-associated pathology through a cell culture and mouse model of murine-adapted scrapie strain RML. In contrast to the role in other neurodegenerative diseases, HSP72 did not alter the prion disease course or amount of prion conversion in either disease model. Chronic wasting disease (CWD) is a naturally occurring, horizontally transmitted prion disease affecting wild and captive cervid populations that is rapidly expanding into new states and countries. Studies investigating the distribution of PrPCWD during early subclinical CWD infection have detected prions in the oropharyngeal lymphoid tissues as early as 1.5 months; however, the complete tissue distribution of PrPCWD immediately following prion exposure and the chronological progression of prion tissue accumulation remains unknown. Here, I show prions initially accumulate in the oropharyngeal lymphoid tissues following mucosal exposure and rapidly disseminate to all systemic lymphoid tissues prior to neuroinvasion. These findings will help better understand the early pathogenesis of CWD prior to clinical disease and potentially identify therapeutic targets. Prion disease diagnosis relies on demonstration of the misfolded isoform by immunodetection, amyloid seeding assays, or animal bioassays, all assays which may require separate sample preparations precluding examination by multiple tests. To address this limitation, I developed a new technique to detect PrPCWD amyloid seeding in fixed paraffin-embedded (FPE) tissues by real-time quaking induced conversion (RT-QuIC). FPE RT-QuIC proved to be more sensitive than IHC for prion detection and the use of RT-QuIC amyloid formation kinetics yielded a semi-quantitative estimate of the prion burden in samples without the cost and time of animal bioassays. The normal cellular prion protein resides in cell membrane lipid rafts, which has been shown to be a site of… Advisors/Committee Members: Hoover, Edward A. (advisor), Zabel, Mark D. (advisor), Avery, Anne (committee member), Tjalkens, Ronald (committee member).

Subjects/Keywords: prions

…78 vii CHAPTER 3 Detection and Quantification of CWD Prions in Fixed Paraffin Embedded… …of genetic material (6,7). Studies characterizing the unique properties of prions… …while PrPSc is used to refer to scrapie prions and PrPCWD used to refer to CWD prions. The… …propagation. Second, the propagation and tissue distribution of prions during early CWD pathogenesis… …x29;. In scrapie, the earliest prions were detected in GALT including oropharyngeal lymphoid…

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APA (6^th Edition):

Hoover, C. E. (2016). Biologic and biochemical features of prion pathogenesis. (Doctoral Dissertation). Colorado State University. Retrieved from http://hdl.handle.net/10217/178959

Chicago Manual of Style (16^th Edition):

Hoover, Clare Elizabeth. “Biologic and biochemical features of prion pathogenesis.” 2016. Doctoral Dissertation, Colorado State University. Accessed January 19, 2021. http://hdl.handle.net/10217/178959.

MLA Handbook (7^th Edition):

Hoover, Clare Elizabeth. “Biologic and biochemical features of prion pathogenesis.” 2016. Web. 19 Jan 2021.

Vancouver:

Hoover CE. Biologic and biochemical features of prion pathogenesis. [Internet] [Doctoral dissertation]. Colorado State University; 2016. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/10217/178959.

Council of Science Editors:

Hoover CE. Biologic and biochemical features of prion pathogenesis. [Doctoral Dissertation]. Colorado State University; 2016. Available from: http://hdl.handle.net/10217/178959

Florida Atlantic University

2. Regmi, Deepika. INVESTIGATING THE AMYLOIDOGENESIS OF A PRION PEPTIDE (106-128).

Degree: MS, 2020, Florida Atlantic University

URL: http://fau.digital.flvc.org/islandora/object/fau:44447

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The misfolding of native, cellular prion protein (PrPc) to a conformationally altered pathogenic isoform, designated scrapie PrPsc, is the main molecular process involved in the… (more)

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The misfolding of native, cellular prion protein (PrPc) to a conformationally altered pathogenic isoform, designated scrapie PrPsc, is the main molecular process involved in the pathogenesis of prion diseases. Prion diseases are marked by the accumulation of conformationally modified forms of cellular prion protein. An N-terminal portion of the prion protein, PrP (106-128), is a 23-residue peptide fragment and is characterized by an amphipathic structure with two domains: a hydrophilic N-terminal domain and a hydrophobic C-terminal domain. In this study, the aggregation characteristics of the PrP (106-128) peptide were investigated using a combination of biophysical approaches. We investigated the effect of different factors including concentrations, pH, and metal ions, on the aggregation of the peptide. Our results demonstrated that the peptide steadily aggregates at concentrations higher than 25 M. The aggregation propensity and fibril formation is higher at pH 7.4 and pH 8.1, and the aggregation is inhibited at pH lower than 6. Furthermore, our results indicate that the Cu2+ has much less effect on the peptide amyloidogenesis, while Zn2+ has a significant influence on the PrP (106-128) amyloidogenesis. We further presented a systematic analysis of the impact of phospholipid liposomes of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-(1’-racglycerol) (POPG) in the absence or presence of cholesterol, on the amyloidogenesis of PrP (106-128). The results showed that POPC vesicles does not significantly influence the aggregation kinetics of the peptide. However, the anionic lipid POPG delays the aggregation in a concentration-dependent manner, whereas the addition of POPG with the cholesterol shows fast kinetics of fibrillization, thus reducing the lag time of the aggregation kinetics. We also monitored the effect of cholesterol and its derivatives including cholesterol-SO4 and DC-cholesterol on PrP (106-128) amyloidogenesis. Our results showed that the cholesterol inhibits the peptide aggregation and delays the formation of fibrils in a concentration-dependent manner. Cholesterol-SO4 dramatically facilitates the aggregation at high concentrations but has the potential to slow down the fibrillization at low concentrations, whereas cationic DC-cholesterol vesicles can effectively inhibit peptide fibril formation at high concentrations.

2020

Degree granted:

Collection: FAU

Advisors/Committee Members: Du, Deguo (Thesis advisor), Florida Atlantic University (Degree grantor), Department of Chemistry and Biochemistry, Charles E. Schmidt College of Science.

Subjects/Keywords: Prion Diseases; Prions – pathogenicity; Amyloid; Peptides; Prions

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APA (6^th Edition):

Regmi, D. (2020). INVESTIGATING THE AMYLOIDOGENESIS OF A PRION PEPTIDE (106-128). (Masters Thesis). Florida Atlantic University. Retrieved from http://fau.digital.flvc.org/islandora/object/fau:44447

Chicago Manual of Style (16^th Edition):

Regmi, Deepika. “INVESTIGATING THE AMYLOIDOGENESIS OF A PRION PEPTIDE (106-128).” 2020. Masters Thesis, Florida Atlantic University. Accessed January 19, 2021. http://fau.digital.flvc.org/islandora/object/fau:44447.

MLA Handbook (7^th Edition):

Regmi, Deepika. “INVESTIGATING THE AMYLOIDOGENESIS OF A PRION PEPTIDE (106-128).” 2020. Web. 19 Jan 2021.

Vancouver:

Regmi D. INVESTIGATING THE AMYLOIDOGENESIS OF A PRION PEPTIDE (106-128). [Internet] [Masters thesis]. Florida Atlantic University; 2020. [cited 2021 Jan 19]. Available from: http://fau.digital.flvc.org/islandora/object/fau:44447.

Council of Science Editors:

Regmi D. INVESTIGATING THE AMYLOIDOGENESIS OF A PRION PEPTIDE (106-128). [Masters Thesis]. Florida Atlantic University; 2020. Available from: http://fau.digital.flvc.org/islandora/object/fau:44447

Harvard University

3. Nako, Entela. Using E. coli as an experimental system to study the behavior of prion-like proteins.

Degree: PhD, Biology, Molecular and Cellular, 2013, Harvard University

URL: http://nrs.harvard.edu/urn-3:HUL.InstRepos:11169790

► Prions are infectious, self-propagating protein aggregates that have been uncovered in evolutionary divergent members of the eukaryotic domain of life. It is not known whether… (more)

Subjects/Keywords: Biology; Bacteria; Prions

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Nako, E. (2013). Using E. coli as an experimental system to study the behavior of prion-like proteins. (Doctoral Dissertation). Harvard University. Retrieved from http://nrs.harvard.edu/urn-3:HUL.InstRepos:11169790

Chicago Manual of Style (16^th Edition):

Nako, Entela. “Using E. coli as an experimental system to study the behavior of prion-like proteins.” 2013. Doctoral Dissertation, Harvard University. Accessed January 19, 2021. http://nrs.harvard.edu/urn-3:HUL.InstRepos:11169790.

MLA Handbook (7^th Edition):

Nako, Entela. “Using E. coli as an experimental system to study the behavior of prion-like proteins.” 2013. Web. 19 Jan 2021.

Vancouver:

Nako E. Using E. coli as an experimental system to study the behavior of prion-like proteins. [Internet] [Doctoral dissertation]. Harvard University; 2013. [cited 2021 Jan 19]. Available from: http://nrs.harvard.edu/urn-3:HUL.InstRepos:11169790.

Council of Science Editors:

Nako E. Using E. coli as an experimental system to study the behavior of prion-like proteins. [Doctoral Dissertation]. Harvard University; 2013. Available from: http://nrs.harvard.edu/urn-3:HUL.InstRepos:11169790

Colorado State University

4. Kane, Sarah. Unraveling prions: the complexities between the prion protein, complement, and B cells in diverse pathogenic settings.

Degree: PhD, Cell and Molecular Biology, 2017, Colorado State University

URL: http://hdl.handle.net/10217/185702

► Prions diseases affect numerous mammalian species and may arise spontaneously, from genetic predisposition of the prion protein PrPC to misfold and aggregate, or from contacted… (more)

▼ Prions diseases affect numerous mammalian species and may arise spontaneously, from genetic predisposition of the prion protein PrPC to misfold and aggregate, or from contacted with prion-contaminated materials. The first described prion disease, Scrapie, manifests in sheep, and records date back to the 18th century. Other mammalian species susceptible to prion diseases include humans, cats, mink, cervids (deer, elk, and moose), and cattle. The term Transmissible Spongiform Encephalopathy (TSE) arose to describe this new class of infectious diseases which exhibit spongiform degeneration in the central nervous system (CNS). TSEs are invariably fatal diseases, and only herd culling or breeding resistance mitigate disease spreading. However, chronic wasting disease (CWD) in cervids represents the first known TSE to occur in free-ranging wildlife, and the apparent facile spread demands strategies to halt its spread and prevent species eradication. Human prion disease characterization dates back to the 1920s. However, the bovine spongiform encephalopathy (BSE or mad cow disease) outbreak and subsequent transmission into a small number of humans in the 1980s and 90s pressed the need to understand the TSE agent. Many researchers since the 1960s postulated protein at least partially comprised the agent, but Stanley Prusiner provided the first scientific evidence of protein composition correlating with infectivity. Further, he coined the term proteinaceous particle, or prion. Follow-up research elegantly highlighted a host protein requisite to cause disease. Researchers now broadly accept the disease mechanism involves prions perverting the cellular prion protein to alter its conformation and join the highly stable growing prion aggregate. Upon peripheral exposure, most prion strains propagate in the lymphoreticular system prior to invading the CNS. Many elegant studies reveal the Complement system promotes initial prion trafficking and propagation in spleen and lymph nodes because mice deficient in various Complement proteins or receptors exhibit delayed or no disease. Once in the LRS, many postulate prions retrogradely infect the brain via sympathetic nerve fibers and the spinal cord. Once in the brain, prions provoke astrogliosis, neurodegeneration, and invariable death. While prion researchers made great strides in characterizing TSEs within a short few decades, many fundamental questions remain unaddressed. For example: what additional host factors foster prion pathogenesis? What is the normal function of the properly-folded, cellular prion protein? Lastly, do prion binding partners provide therapeutic targets? Data presented in this dissertation highlight crucial roles for Complement regulatory protein Factor H and Complement receptor CD21 in Scrapie pathogenesis, suggest C1q may strain-specifically impact prion disease, highlight PrPC as a crucial mediator in the adaptive immune system, and provide potential therapeutic tools and targets to combat prion disease. Advisors/Committee Members: Zabel, Mark (advisor), Bamburg, James (committee member), Tjalkens, Ronald (committee member), Avery, Anne (committee member).

Subjects/Keywords: nanobodies; complement; prions

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Kane, S. (2017). Unraveling prions: the complexities between the prion protein, complement, and B cells in diverse pathogenic settings. (Doctoral Dissertation). Colorado State University. Retrieved from http://hdl.handle.net/10217/185702

Chicago Manual of Style (16^th Edition):

Kane, Sarah. “Unraveling prions: the complexities between the prion protein, complement, and B cells in diverse pathogenic settings.” 2017. Doctoral Dissertation, Colorado State University. Accessed January 19, 2021. http://hdl.handle.net/10217/185702.

MLA Handbook (7^th Edition):

Kane, Sarah. “Unraveling prions: the complexities between the prion protein, complement, and B cells in diverse pathogenic settings.” 2017. Web. 19 Jan 2021.

Vancouver:

Kane S. Unraveling prions: the complexities between the prion protein, complement, and B cells in diverse pathogenic settings. [Internet] [Doctoral dissertation]. Colorado State University; 2017. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/10217/185702.

Council of Science Editors:

Kane S. Unraveling prions: the complexities between the prion protein, complement, and B cells in diverse pathogenic settings. [Doctoral Dissertation]. Colorado State University; 2017. Available from: http://hdl.handle.net/10217/185702

University of Alberta

5. Joy, Shaon. New Aspects of Nazarov Reaction: Additive Effects, Gold Catalysis and Application Toward the Synthesis of Taxinine.

Degree: PhD, Department of Chemistry, 2013, University of Alberta

URL: https://era.library.ualberta.ca/files/r494vk698

► Methods involving efficient and stereoselective carbon-carbon bond formation enable chemists to synthesize bioactive natural products and drugs. The Nazarov reaction is a versatile tool for… (more)

▼ Methods involving efficient and stereoselective carbon-carbon bond formation enable chemists to synthesize bioactive natural products and drugs. The Nazarov reaction is a versatile tool for the construction of functionalized cyclopentenones. This 4π-electrocyclization provides easy and efficient access to multi-substituted cyclopentenones with excellent stereocontrol at two contiguous ring carbons and opportunities to link to additional bond-forming events. Typically, the Nazarov cyclization involves 1,4-pentadien-3-ones. However, development of unconventional initiation protocols to access the key pentadienyl cation in the Nazarov reaction has gained considerable popularity over the past decade. Chapter 1 describes the recent activity in the area of alternate activation protocols for Nazarov cyclization. One rapidly expanding area of homogeneous gold catalysis is the Au(I) catalyzed rearrangements of propargylic carboxylates, leading to domino reaction sequences. Chapter 2 discusses the synthesis of bridged bicyclic enynyl acetates and their use as dienone surrogates. The compounds undergo a [3,3]-rearrangement followed by a 4π-electrocyclization under Au(I) catalysis to form cyclopentenones in a regioselective fashion. Chapter 3 recounts our comprehensive investigation on the effects of additives in the silicon-directed Nazarov cyclization. We have found that the presence of hydroxylic additives can lead to facile and clean cyclizations of β-silyl substituted dienones. Successful cyclization of some lightly substituted dienones have been reported, which are otherwise highly unreactive under standard conditions. In chapter 4 our continued efforts toward the synthesis of taxinine are reported. The completion of the synthesis requires a six-membered ring annulation method to a previously established bicyclo[5.3.1]undecene core. Our attempts at the six-membered ring annulation involving a late-stage C-H insertion via metal-carbenoid chemistry has been presented. Some novel reactivities of the late-stage intermediates have also been explored. Prion diseases are a group of infectious neurodegenerative disorders that affect both humans and animals. They are invariably fatal due to the lack of proper treatment or cure. Current research relies heavily on the hypothesis that prion pathogenesis coincides with the cellular prion protein (PrPC) undergoing conformational change to the β-sheet enriched isoform PrPSc. Chapter 5 elaborates our efforts in the development of multivalent PrPSc binding compounds. Three classes of compounds were synthesized and tested for anti-prion activity.

Subjects/Keywords: Nazarov; Taxinine; Gold Catalysis; Prions

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Joy, S. (2013). New Aspects of Nazarov Reaction: Additive Effects, Gold Catalysis and Application Toward the Synthesis of Taxinine. (Doctoral Dissertation). University of Alberta. Retrieved from https://era.library.ualberta.ca/files/r494vk698

Chicago Manual of Style (16^th Edition):

Joy, Shaon. “New Aspects of Nazarov Reaction: Additive Effects, Gold Catalysis and Application Toward the Synthesis of Taxinine.” 2013. Doctoral Dissertation, University of Alberta. Accessed January 19, 2021. https://era.library.ualberta.ca/files/r494vk698.

MLA Handbook (7^th Edition):

Joy, Shaon. “New Aspects of Nazarov Reaction: Additive Effects, Gold Catalysis and Application Toward the Synthesis of Taxinine.” 2013. Web. 19 Jan 2021.

Vancouver:

Joy S. New Aspects of Nazarov Reaction: Additive Effects, Gold Catalysis and Application Toward the Synthesis of Taxinine. [Internet] [Doctoral dissertation]. University of Alberta; 2013. [cited 2021 Jan 19]. Available from: https://era.library.ualberta.ca/files/r494vk698.

Council of Science Editors:

Joy S. New Aspects of Nazarov Reaction: Additive Effects, Gold Catalysis and Application Toward the Synthesis of Taxinine. [Doctoral Dissertation]. University of Alberta; 2013. Available from: https://era.library.ualberta.ca/files/r494vk698

Université de Sherbrooke

6. Forget, Karolyn. Les agrégats de la protéine p53 comportent certaines propriétés des prions.

Degree: 2013, Université de Sherbrooke

URL: http://hdl.handle.net/11143/6301

► Les maladies à prion sont un cas unique de pathologie où l’agent infectieux, le prion, est une protéine. La protéine prion possède plusieurs caractéristiques qui… (more)

▼ Les maladies à prion sont un cas unique de pathologie où l’agent infectieux, le prion, est une protéine. La protéine prion possède plusieurs caractéristiques qui la rendent particulière vis-à-vis d’autres protéines cellulaires, telles que sa capacité à agréger et à transmettre sa conformation agrégée à la protéine soluble ainsi que la transmission des agrégats de la protéine d’une cellule à l’autre et d’un organisme à un autre. De plus en plus, on associe l’agrégation de protéines à différentes maladies humaines, comme les maladies d’Alzheimer, de Parkinson et le diabète de type 2. Certaines protéines impliquées dans ces pathologies font partie des prionoïdes, une catégorie réservée aux protéines aux propriétés agrégatives qui démontrent certaines des caractéristiques associées aux prions. Récemment, la protéine p53, un facteur de transcription fortement impliqué dans le cancer, a été montrée comme étant capable d’agréger in vitro. Une accumulation de la protéine a également été observée dans des cellules tumorales, laissant croire que l’agrégation de p53 se produit également in vivo, et pourrait avoir un rôle dans le développement du cancer. Ces observations portent à croire que la protéine p53 pourrait elle aussi faire partie des prionoïdes. L’objectif de cette étude est donc de montrer que la protéine p53 possède certaines des caractéristiques des prions. Pour ce faire, la protéine p53 recombinante a été produite pour former des agrégats de p53 et ces agrégats ont été utilisés pour déterminer si la protéine démontre des caractères prionoïdes. Les résultats obtenus montrent une agrégation in vitro de p53WT pleine longueur ainsi que de sa forme tronquée, p53C. De plus, des cellules en culture sont capables d’internaliser ces agrégats, qui co-agrègent ensuite avec la protéine p53 endogène de ces cellules. Enfin, nos résultats montrent clairement que l’internalisation des agrégats par les cellules se fait par la macropinocytose. Nous avons donc réussi à prouver que la protéine p53 agit comme un prion puisqu’elle s’agrège spontanément, ses agrégats sont internalisés par des cellules en culture et sont capables de co-agréger avec la protéine soluble. Advisors/Committee Members: Roucou, Xavier (advisor).

Subjects/Keywords: Agrégation protéique; P53; Prions

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Forget, K. (2013). Les agrégats de la protéine p53 comportent certaines propriétés des prions. (Masters Thesis). Université de Sherbrooke. Retrieved from http://hdl.handle.net/11143/6301

Chicago Manual of Style (16^th Edition):

Forget, Karolyn. “Les agrégats de la protéine p53 comportent certaines propriétés des prions.” 2013. Masters Thesis, Université de Sherbrooke. Accessed January 19, 2021. http://hdl.handle.net/11143/6301.

MLA Handbook (7^th Edition):

Forget, Karolyn. “Les agrégats de la protéine p53 comportent certaines propriétés des prions.” 2013. Web. 19 Jan 2021.

Vancouver:

Forget K. Les agrégats de la protéine p53 comportent certaines propriétés des prions. [Internet] [Masters thesis]. Université de Sherbrooke; 2013. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/11143/6301.

Council of Science Editors:

Forget K. Les agrégats de la protéine p53 comportent certaines propriétés des prions. [Masters Thesis]. Université de Sherbrooke; 2013. Available from: http://hdl.handle.net/11143/6301

East Carolina University

7. Gangula, Manasa. Design and Quantitation of Membrane Binding Lipid Anchors : Exploring Prion-Prion Interactions on Membrane Surfaces.

Degree: 2011, East Carolina University

URL: http://libres.uncg.edu/ir/listing.aspx?styp=ti&id=13970

► The prion protein (PrP) is an endogenous metal binding protein present in the neuronal cells of the central nervous system. Prion is associated with a… (more)

▼ The prion protein (PrP) is an endogenous metal binding protein present in the neuronal cells of the central nervous system. Prion is associated with a class of neurodegenerative diseases known as transmissible spongiform encephalopathies. The C-terminal region of the prion protein is anchored to the cell surface by means of a glycophosphatidylinositol (GPI) anchor[superscript]19. Studies indicate that PrP self-recognition may be an important factor in both the normal function and misfunction of PrP. Elucidating the molecular basis for PrP-PrP interactions in the context of its membrane bound state will help in understanding the normal function of PrP such as the signaling mechanism for endocytosis and the factors that influence disease causing structural changes. Fluorescently labeled models of prion protein were previously developed to investigate PrP-PrP interactions and metal binding at molecular level. Peptides constituting the metal binding region were anchored to small unilamellar vesicles (liposomes) and PrP-PrP interactions were studied as a function of added metal45. Anchoring the peptides is an essential step to understand the protein interactions in the context of a cell surface. The main objective of this research is to prepare a molecule capable of anchoring the majority of a PrP sample to a liposome and develop a spin-label based assay to determine the percentage of molecules anchored to the liposome surface. Four lipophilic molecules containing a nitroxide spin-label have been synthesized and their electron paramagnetic resonance (EPR) spectra collected in the presence and absence of liposomes. The EPR spectrum of the nitroxide is very sensitive to the motion of the spin label and the proximity to other spin labeled molecules. The anchor with a linear chain of sixteen carbon atoms showed the most dramatic changes in the EPR spectrum and is likely the best anchor. We are planning to use a paramagnetic relaxation agent that aids in the quantitation and fluorescent compounds which aid in determining where the spin-labeled molecules localize. The spin-label methodology will allow us to conduct more quantitative experiments on PrP interactions with respect to metal binding change in temperature pH etc. ; Biochemistry, Analytical chemistry Advisors/Committee Members: Colin S. Burns (advisor).

Subjects/Keywords: Prions; Lipids; Cell membranes; Peptides

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APA (6^th Edition):

Gangula, M. (2011). Design and Quantitation of Membrane Binding Lipid Anchors : Exploring Prion-Prion Interactions on Membrane Surfaces. (Masters Thesis). East Carolina University. Retrieved from http://libres.uncg.edu/ir/listing.aspx?styp=ti&id=13970

Chicago Manual of Style (16^th Edition):

Gangula, Manasa. “Design and Quantitation of Membrane Binding Lipid Anchors : Exploring Prion-Prion Interactions on Membrane Surfaces.” 2011. Masters Thesis, East Carolina University. Accessed January 19, 2021. http://libres.uncg.edu/ir/listing.aspx?styp=ti&id=13970.

MLA Handbook (7^th Edition):

Gangula, Manasa. “Design and Quantitation of Membrane Binding Lipid Anchors : Exploring Prion-Prion Interactions on Membrane Surfaces.” 2011. Web. 19 Jan 2021.

Vancouver:

Gangula M. Design and Quantitation of Membrane Binding Lipid Anchors : Exploring Prion-Prion Interactions on Membrane Surfaces. [Internet] [Masters thesis]. East Carolina University; 2011. [cited 2021 Jan 19]. Available from: http://libres.uncg.edu/ir/listing.aspx?styp=ti&id=13970.

Council of Science Editors:

Gangula M. Design and Quantitation of Membrane Binding Lipid Anchors : Exploring Prion-Prion Interactions on Membrane Surfaces. [Masters Thesis]. East Carolina University; 2011. Available from: http://libres.uncg.edu/ir/listing.aspx?styp=ti&id=13970

Texas Medical Center

8. Khan, Uffaf. Metabolic profiling of prions in the gastro-intestinal tract.

Degree: MS, 2015, Texas Medical Center

URL: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/624

► Metabolic profiling of prions in the gastro-intestinal tract Uffaf Khan, B.S. Thesis Advisor: Claudio Soto, Ph.D. Abstract Prion diseases, also known as transmissible spongiform… (more)

Subjects/Keywords: Prions; TSE's; scrapie; PMCA; radiolabeled prions; Medicine and Health Sciences; Neurosciences

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Khan, U. (2015). Metabolic profiling of prions in the gastro-intestinal tract. (Thesis). Texas Medical Center. Retrieved from https://digitalcommons.library.tmc.edu/utgsbs_dissertations/624

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Khan, Uffaf. “Metabolic profiling of prions in the gastro-intestinal tract.” 2015. Thesis, Texas Medical Center. Accessed January 19, 2021. https://digitalcommons.library.tmc.edu/utgsbs_dissertations/624.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Khan, Uffaf. “Metabolic profiling of prions in the gastro-intestinal tract.” 2015. Web. 19 Jan 2021.

Vancouver:

Khan U. Metabolic profiling of prions in the gastro-intestinal tract. [Internet] [Thesis]. Texas Medical Center; 2015. [cited 2021 Jan 19]. Available from: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/624.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Khan U. Metabolic profiling of prions in the gastro-intestinal tract. [Thesis]. Texas Medical Center; 2015. Available from: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/624

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

9. Fabiana Andrade Caetano. Estudo dos ligantes da proteína prion celular com ênfase em estress inducible protein 1: modificação pós-traducional, tráfego e sinalização.

Degree: 2010, Universidade Federal de Minas Gerais

URL: http://hdl.handle.net/1843/EJAO-8JKME8

► A proteina prion celular (PrPC) constitui uma plataforma na membrana plasmatica capaz de interagir com diversos ligantes mediando a reuniao de complexos de sinalizacao na… (more)

▼ A proteina prion celular (PrPC) constitui uma plataforma na membrana plasmatica capaz de interagir com diversos ligantes mediando a reuniao de complexos de sinalizacao na superficie celular. Um dos ligantes mais bem descritos para PrPC e a co-chaperonina Stress Inducible Protein1 ou STI1. STI1 e secretada por astrocitos e interage com PrPC na superficie neuronal induzindo neuritogenese e neuroprotecao por ativacao de vias de sinalizacao diferentes. Embora pouco se saiba sobre os mecanismos de secrecao de STI1, acredita-se que este processo e fundamental na regulacao das funcoes neurotroficas medidas pela interacao STI1- PrPC . A STI1 intracelular tem papel importante na reuniao do complexo Hsp70-Hsp90 sendo portanto, considerada uma proteina com funcoes intra e extracelulares. Na tentativa de elucidarmos mecanismos envolvido com as funcoes de STI1, novos ligantes de STI1 foram identificados em um ensaio de duplo hibrido. Dentre os principais ligantes, estao as proteinas da via de SUMOilacao, cujas interacoes de STI1 com os componentes desta via foram confirmadas neste trabalho. Nos mostramos que STI1 e SUMOilada por SUMO1 e SUMO3, sendo PIAS1 a E3 ligase especifica para este processo. A interacao de STI1 com PIAS1 e SUMO3 levou ao aumento da localizacao nuclear de STI1. Uma vez no nucleo, STI1 foi direcionada para os corpos PML (do ingles Pro-Myelocytic Leukaemia), de forma dependente de PIAS1, onde se co-localizou com SUMO1 e SUMO3. O estresse celular por Choque Termico nao induziu alteracoes na distribuicao celular de STI1, mesmo quando as proteinas da via de SUMOilacao foram co-expressas. Por outro lado, nos mostramos que o dano no DNA por irradiacao ionizante induziu o translocacao de STI1 para o nucleo, onde ela se co-localizou parcialmente com os Foci. Em conjunto os nossos resultados mostram que STI1 e preferencialmente modificada por SUMO3 e PIAS1. O seu direcionamento para os corpos PML, mediado por PIAS1, e translocacao nuclear induzido por estresse genotoxico sugerem o envolvimento de STI1 na via de reparo ao DNA. Tendo em vista a alteracao na distribuicao celular induzida pela sua interacao com as proteinas da via de SUMOilacao, novos estudos estao sendo realizados para avaliar o papel desta via sobre a secrecao de STI1. Em relacao ao contexto extracelular, nos mostramos que STI1 ao se ligar a PrPC na membrana induz a internalizacao desta ultima proteina. A internalizacao de PrPC foi fundamental para a regulacao da ativacao de ERK1/2, mas nao de PKA, induzida pela sua interacao com STI1. STI1 tambem foi endocitada, de forma independente da presenca de PrPC. Atraves de microscopia em tempo real, utilizando marcadores de vias endociticas, nos mostramos que STI1 e internalizada por duas vias: parte de STI1 e internalizada por vias dependentes de lipide rafts, enquanto uma segunda fracao e internalizada pela via classica, dependente de clatrina. Uma vez internalizada STI1 segue uma via intracelular distinta daquela vista para PrPC, sendo diretamente direcionada para vesiculas acidicas sem passar pelos… Advisors/Committee Members: Marco Antonio Maximo Prado, Vania Ferreira Prado, Marco Antonio Maximo Prado, Vilma Regina Martins, Silvio Marques Zanata, Marcus Vinicius Gomez, Fabiola Mara Ribeiro.

Subjects/Keywords: Prions Teses.; Farmacologia Teses.; Stress Teses.

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Caetano, F. A. (2010). Estudo dos ligantes da proteína prion celular com ênfase em estress inducible protein 1: modificação pós-traducional, tráfego e sinalização. (Thesis). Universidade Federal de Minas Gerais. Retrieved from http://hdl.handle.net/1843/EJAO-8JKME8

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Caetano, Fabiana Andrade. “Estudo dos ligantes da proteína prion celular com ênfase em estress inducible protein 1: modificação pós-traducional, tráfego e sinalização.” 2010. Thesis, Universidade Federal de Minas Gerais. Accessed January 19, 2021. http://hdl.handle.net/1843/EJAO-8JKME8.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Caetano, Fabiana Andrade. “Estudo dos ligantes da proteína prion celular com ênfase em estress inducible protein 1: modificação pós-traducional, tráfego e sinalização.” 2010. Web. 19 Jan 2021.

Vancouver:

Caetano FA. Estudo dos ligantes da proteína prion celular com ênfase em estress inducible protein 1: modificação pós-traducional, tráfego e sinalização. [Internet] [Thesis]. Universidade Federal de Minas Gerais; 2010. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/1843/EJAO-8JKME8.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Caetano FA. Estudo dos ligantes da proteína prion celular com ênfase em estress inducible protein 1: modificação pós-traducional, tráfego e sinalização. [Thesis]. Universidade Federal de Minas Gerais; 2010. Available from: http://hdl.handle.net/1843/EJAO-8JKME8

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

10. Schutt, Charles. Prion Strain Conformational Stability and the Role of PrPc in Prion Strain Interference.

Degree: M.S. in Medical Microbiology and Immunology, Medical Microbiology and Immunology (graduate program), 2011, Creighton University

URL: http://hdl.handle.net/10504/17148

► Prions are the causative agent of transmissible spongiform encephalopathies (TSEs), a group of neurodegenerative diseases characterized by the accumulation of PrPSc, an abnormal conformation of… (more)

▼ Prions are the causative agent of transmissible spongiform encephalopathies (TSEs), a group of neurodegenerative diseases characterized by the accumulation of PrPSc, an abnormal conformation of the normal host protein PrPC. Different conformations of PrPSc are thought to be the cause of different phenotypes of TSE disease which are called prion strains. These different prion strains can interact with one another. Prion strain interference is the ability of a long incubation period strain (blocking strain) to extend the incubation period or block a shorter incubation period strain (superinfecting strain) from causing disease. The mechanism of prion strain interference is of interest because this is one of the few known mechanisms where the ability of a prion strain to cause disease is attenuated.|To determine if a single blocking strain can interfere with multiple superinfecting strains,we inoculated hamsters in the sciatic nerve with uninfected or DY TME-infected brain homogenate and superinfected 120 days later with brain homogenate from one of three superinfecting strains. The superinfecting strain caused disease in all hamsters initially inoculated with uninfected brain homogenate. DY TME caused disease in all hamsters initially inoculated with DY TME. This demonstrates that a single blocking strain has the ability to interfere with several superinfecting strains, suggesting that prion strain interference may be a property common to many different prion strains.|To determine if prion strain interference can occur through a natural route of inoculation, hamsters were fed DY TME-infected food pellets and then superinfected with HY TME-infected food pellets. HY TME caused disease in all hamsters. However, with 120 days between inoculations, DY TME extended the incubation period of HY TME, showing that prion strain interference can occur following per os inoculation, suggesting that prion strain interference may be part of the natural biology of TSEs. |To determine if prion strain interference was due to depletion of PrPC by the blocking strain, I developed an assay that isolated PrPC from PrPSc. We inoculated DY TME or uninfected brain homogenate into the sciatic nerve of hamsters, and different time points post inoculation, the spinal cord between vertebrae T10-T13 was removed, dissected into ipsilateral and contralateral halves. PrPC was isolated from each half of the spinal cord and the concentration of PrPC was standardized to the concentration of total protein. I could not detect any change in PrPC level over time, between each half of the spinal cord or between DY TMEinfected and uninfected spinal cords. While there was no change in PrPC level, I confirmed DY PrPSc accumulation in the spinal cord over time. This data shows that PrPC depletion is not part of the mechanism of prion strain interference. |I also developed an assay to differentiate different hamster prions strains based on their conformational stability. Conformational stability is the ability of PrPSc to resist being denatured by a chaotropic… Advisors/Committee Members: Bartz, Jason C. (advisor), Schutt, Charles (cuauthor).

Subjects/Keywords: Prions – physiology; Host-Pathogen Interactions; Neurons – metabolism

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APA (6^th Edition):

Schutt, C. (2011). Prion Strain Conformational Stability and the Role of PrPc in Prion Strain Interference. (Masters Thesis). Creighton University. Retrieved from http://hdl.handle.net/10504/17148

Chicago Manual of Style (16^th Edition):

Schutt, Charles. “Prion Strain Conformational Stability and the Role of PrPc in Prion Strain Interference.” 2011. Masters Thesis, Creighton University. Accessed January 19, 2021. http://hdl.handle.net/10504/17148.

MLA Handbook (7^th Edition):

Schutt, Charles. “Prion Strain Conformational Stability and the Role of PrPc in Prion Strain Interference.” 2011. Web. 19 Jan 2021.

Vancouver:

Schutt C. Prion Strain Conformational Stability and the Role of PrPc in Prion Strain Interference. [Internet] [Masters thesis]. Creighton University; 2011. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/10504/17148.

Council of Science Editors:

Schutt C. Prion Strain Conformational Stability and the Role of PrPc in Prion Strain Interference. [Masters Thesis]. Creighton University; 2011. Available from: http://hdl.handle.net/10504/17148

Texas A&M University

11. Anand, Ashish. Development of a bio-sensing technique for the detection of prions in foods.

Degree: MS, Biological and Agricultural Engineering, 2005, Texas A&M University

URL: http://hdl.handle.net/1969.1/1503

► An affinity based bio-sensing technique was developed using an anti-transmissible spongiform encephalopathy monoclonal antibody as a bio-recognition molecule. Fluorescein iso-thio-cynate (FITC), labeled with a prion… (more)

▼ An affinity based bio-sensing technique was developed using an anti-transmissible spongiform encephalopathy monoclonal antibody as a bio-recognition molecule. Fluorescein iso-thio-cynate (FITC), labeled with a prion epitope (QYQRES), was used as a decoy for prions. Experiments done in 0.1M phosphate buffer revealed that the dye fluorescence increased with the pH of the buffer and was influenced by solvent polarity. Binding studies conducted at pH 6, 7, and 8 showed that the optimum pH for the antibody-decoy binding was 7. Maximum differences between control and antibody samples were observed at pH 7. The optimum incubation time was found to be less than 4 hours for the control, antibody, and the prion samples at room temperature. Prion detection curves were established at 4 and 10 nM antibody decoy concentrations. The lowest detectable prion concentration in phosphate buffer was 8 nM. Experimental conditions determined in the phosphate buffer were used to implement the technique in gelatin and baby formula. Prion detection curves were generated in 0.01, 0.4, 1.0 and 2.0 mg/ml of gelatin solution. The gelatin interfered with the binding and the displacement reaction of antibody, decoy and prion. Addition of an anionic surfactant, sodium dodecyl sulfate (SDS) at 0.3 mg/ml to gelatin samples facilitated prion detection in gelatin. The lowest detectable concentration of prion in gelatin was 0.5 nM at 0.4mg/ml gelatin. The baby formula samples produced light scattering and the intrinsic peak of baby formula at 526nm interfered with the dye peak at 514nm. Serial dilutions of baby formula were done to reduce the interference. Prion detection curves were then obtained at 1.31 and 5.34 mg/ml baby formula and 0.454 mg/ml of Triton-X-100 was added to the baby formula samples. The lowest detectable concentration of prion was 2 nM for baby formula. This developed bio-sensing technique can be used to detect prion in gelatin and baby formula solutions. Addition of surfactants assisted prion detection in foods, while high concentrations of gelatin and baby formula had an adverse effect on the detection system. Advisors/Committee Members: Castell-Perez, Elena (advisor), Moreira, Rosana (advisor), Coté, Gerard (committee member), Good, Theresa (committee member).

Subjects/Keywords: Biosensor; Prions; Foods

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Anand, A. (2005). Development of a bio-sensing technique for the detection of prions in foods. (Masters Thesis). Texas A&M University. Retrieved from http://hdl.handle.net/1969.1/1503

Chicago Manual of Style (16^th Edition):

Anand, Ashish. “Development of a bio-sensing technique for the detection of prions in foods.” 2005. Masters Thesis, Texas A&M University. Accessed January 19, 2021. http://hdl.handle.net/1969.1/1503.

MLA Handbook (7^th Edition):

Anand, Ashish. “Development of a bio-sensing technique for the detection of prions in foods.” 2005. Web. 19 Jan 2021.

Vancouver:

Anand A. Development of a bio-sensing technique for the detection of prions in foods. [Internet] [Masters thesis]. Texas A&M University; 2005. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/1969.1/1503.

Council of Science Editors:

Anand A. Development of a bio-sensing technique for the detection of prions in foods. [Masters Thesis]. Texas A&M University; 2005. Available from: http://hdl.handle.net/1969.1/1503

Université Laval

12. Lauruol, Florian. Étude des propriétés prioniques de la huntingtine mutée dans des modèles in vitro et in vivo.

Degree: 2019, Université Laval

URL: http://hdl.handle.net/20.500.11794/35845

► La maladie de Huntington (MH) est une maladie neurodégénérative causée par la mutation du gène codant la protéine huntingtine (HTT). Cette protéine, exprimée par toutes… (more)

▼ La maladie de Huntington (MH) est une maladie neurodégénérative causée par la mutation du gène codant la protéine huntingtine (HTT). Cette protéine, exprimée par toutes les cellules de l'organisme, peut adopter une forme mutée qui lui confère un aspect toxique. Dans les cellules, la mHTT va s'agréger et former di érentes structures dont des agrégats, marqueurs distinctifs de la maladie, ou des brilles. Dans le cerveau, la présence de la mHTT va causer une mort neuronale dramatique entraînant, à l'échelle de l'individu, une panoplie de troubles moteurs, cognitifs et psychiatriques. Depuis plusieurs années des études tendent à démontrent que la mHTT peut se propager de cellules à cellules et corrompre la HTT non mutée tel un prion. Pour mon projet de recherche, j'ai ainsi investigué les propriétés prioniques de la mHTT sous sa forme fibrillaire particulièrement toxique. Des fibrilles synthétiques contenant la mutation pathologique ont été utilisées pour infecter des cellules en culture et des souris. De cette manière, nous avons démontré la capacité des fibrilles à se propager et à provoquer des dommages divers dans 3 types de cellules humaines. La présence des fibrilles a également induit l'agrégation de la forme non mutée de la HTT endogène, normalement présente dans les cellules. Chez la souris, ces résultats ont été confirmés suite à l'injection des fibrilles dans le cerveau des animaux. La présence des fibrilles dans le système nerveux central des souris sauvages a provoqué la manifestation de signes caractéristiques de la MH (troubles cognitifs et moteurs). De plus, une apparition de déficits moteurs et cognitifs qui s'apparentent à la maladie a été observée chez des souris R6/2, modèle transgénique de la MH, suite à l'injection des fibrilles. Les résultats de mon projet de recherche renforcent ainsi l'hypothèse prionique de la mHTT et appuient l'hypothèse que ces propriétés pourraient être impliquées dans la physiopathologie de la MH. Advisors/Committee Members: Cicchetti, Francesca.

Subjects/Keywords: Chorée de Huntington; Prions (Virologie); Protéines

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Lauruol, F. (2019). Étude des propriétés prioniques de la huntingtine mutée dans des modèles in vitro et in vivo. (Thesis). Université Laval. Retrieved from http://hdl.handle.net/20.500.11794/35845

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Lauruol, Florian. “Étude des propriétés prioniques de la huntingtine mutée dans des modèles in vitro et in vivo.” 2019. Thesis, Université Laval. Accessed January 19, 2021. http://hdl.handle.net/20.500.11794/35845.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Lauruol, Florian. “Étude des propriétés prioniques de la huntingtine mutée dans des modèles in vitro et in vivo.” 2019. Web. 19 Jan 2021.

Vancouver:

Lauruol F. Étude des propriétés prioniques de la huntingtine mutée dans des modèles in vitro et in vivo. [Internet] [Thesis]. Université Laval; 2019. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/20.500.11794/35845.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Lauruol F. Étude des propriétés prioniques de la huntingtine mutée dans des modèles in vitro et in vivo. [Thesis]. Université Laval; 2019. Available from: http://hdl.handle.net/20.500.11794/35845

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Wollongong

13. Zeineddine, Rafaa. The role of the prion-like protein SOD1 and macropinocytosis in the propagation of disease in ALS; an infectious idea.

Degree: PhD, 2016, University of Wollongong

URL: 060105 Cell Neurochemistry, 060108 Protein Trafficking, 060110 Receptors and Membrane Biology, 060199 Biochemistry and Cell Biology not elsewhere classified ; https://ro.uow.edu.au/theses/4879

► With the onset of the rapidly increasing population, the impact of age related neurodegenerative diseases including Amyotrophic lateral sclerosis, Alzheimer’s disease, Creutzfeldt-Jakob disease, Parkinson’s… (more)

▼ With the onset of the rapidly increasing population, the impact of age related neurodegenerative diseases including Amyotrophic lateral sclerosis, Alzheimer’s disease, Creutzfeldt-Jakob disease, Parkinson’s disease, Huntington’s disease and frontotemporal dementia is becoming a predominant health and economic concern. Amyotrophic lateral sclerosis (ALS) is a devastating neuromuscular degenerative disease that currently has no effective treatment or therapeutics. ALS is characterised by a focal onset of motor neuron loss, followed by contiguous outward spreading of pathology throughout the nervous system, resulting in paralysis and death generally within a few years after diagnosis. The mechanisms underlying neurodegeneration of motor neurons and disease progression are currently unknown; however, current evidence implicates a range of cellular mechanisms. These mechanisms include, deficient protein quality control, aberrant RNA metabolism, oxidative stress, endoplasmic reticulum stress, glutamate excitotoxicity, mitochondrial dysfunction, fragmentation of the Golgi apparatus, activated glia, axonal transport defects and neuroinflammation. These dysfunctional cellular pathways may be associated with the protein aggregates that are hallmarks of ALS pathology. However, the dysfunction in several cellular processes does not explain the spreading of pathology, here the aberrant release and uptake of toxic proteins including SOD1 and TDP-43 and their subsequent accumulation and deposition in motor neurons may contribute. Given this hypothesis, the work presented in this thesis aimed to further examine the role of SOD1 and TDP-43 in the propagation of neurodegeneration in ALS, and investigate whether the proteins exhibit prion-like properties. The term “Prion-like” as used here refers to the misfolding and aggregation of a disease specific protein that subsequently escapes the cellular environment and seeds aggregation in a naïve cell. The main aims of this thesis were to: investigate the mechanisms underpinning the uptake of SOD1 aggregates into murine NSC-34 cells (Chapter 2); Examine the subsequent release of SOD1 into the cytosol, detect released extracellular SOD1, and observe for secreted SOD1 internalisation into NSC‐34 motor neurons, then identify and quantify seeding activity in recipient cells expressing SOD1 and characterise this interaction using a novel flow cytometry method to quantify protein aggregation; Flow cytometric characterisation of inclusions and trafficking (FloIT) (Chapter 3); determine whether exogenous recombinant SOD1 protein aggregates can induce and/or contribute to TDP-43 pathology (Chapter 4); determine if SOD1 aggregates can enter humanised models of motor neurons via the same mechanism of action using both iPSC derived motor neurons and primary neurons (Chapter 5).

Subjects/Keywords: ALS; SOD1; MND; prions; protein misfolding

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Zeineddine, R. (2016). The role of the prion-like protein SOD1 and macropinocytosis in the propagation of disease in ALS; an infectious idea. (Doctoral Dissertation). University of Wollongong. Retrieved from 060105 Cell Neurochemistry, 060108 Protein Trafficking, 060110 Receptors and Membrane Biology, 060199 Biochemistry and Cell Biology not elsewhere classified ; https://ro.uow.edu.au/theses/4879

Chicago Manual of Style (16^th Edition):

Zeineddine, Rafaa. “The role of the prion-like protein SOD1 and macropinocytosis in the propagation of disease in ALS; an infectious idea.” 2016. Doctoral Dissertation, University of Wollongong. Accessed January 19, 2021. 060105 Cell Neurochemistry, 060108 Protein Trafficking, 060110 Receptors and Membrane Biology, 060199 Biochemistry and Cell Biology not elsewhere classified ; https://ro.uow.edu.au/theses/4879.

MLA Handbook (7^th Edition):

Zeineddine, Rafaa. “The role of the prion-like protein SOD1 and macropinocytosis in the propagation of disease in ALS; an infectious idea.” 2016. Web. 19 Jan 2021.

Vancouver:

Zeineddine R. The role of the prion-like protein SOD1 and macropinocytosis in the propagation of disease in ALS; an infectious idea. [Internet] [Doctoral dissertation]. University of Wollongong; 2016. [cited 2021 Jan 19]. Available from: 060105 Cell Neurochemistry, 060108 Protein Trafficking, 060110 Receptors and Membrane Biology, 060199 Biochemistry and Cell Biology not elsewhere classified ; https://ro.uow.edu.au/theses/4879.

Council of Science Editors:

Zeineddine R. The role of the prion-like protein SOD1 and macropinocytosis in the propagation of disease in ALS; an infectious idea. [Doctoral Dissertation]. University of Wollongong; 2016. Available from: 060105 Cell Neurochemistry, 060108 Protein Trafficking, 060110 Receptors and Membrane Biology, 060199 Biochemistry and Cell Biology not elsewhere classified ; https://ro.uow.edu.au/theses/4879

University of Manitoba

14. Martin, Matthew. Characterization of AAVrh.10 as a vector to deliver long-lasting genetic constructs into neurons of neonatal mice following intravenous injection.

Degree: Medical Microbiology and Infectious Diseases, 2019, University of Manitoba

URL: http://hdl.handle.net/1993/34637

► Prion diseases are a fatal neurodegenerative disease caused by the misfolding of the cellular prion protein, PrPC into an infectious isoform, PrPSc. Accumulation of this… (more)

Subjects/Keywords: Adeno-associated viruses; Prions; Neurodegeneration; Viral Therapy

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Martin, M. (2019). Characterization of AAVrh.10 as a vector to deliver long-lasting genetic constructs into neurons of neonatal mice following intravenous injection. (Masters Thesis). University of Manitoba. Retrieved from http://hdl.handle.net/1993/34637

Chicago Manual of Style (16^th Edition):

Martin, Matthew. “Characterization of AAVrh.10 as a vector to deliver long-lasting genetic constructs into neurons of neonatal mice following intravenous injection.” 2019. Masters Thesis, University of Manitoba. Accessed January 19, 2021. http://hdl.handle.net/1993/34637.

MLA Handbook (7^th Edition):

Martin, Matthew. “Characterization of AAVrh.10 as a vector to deliver long-lasting genetic constructs into neurons of neonatal mice following intravenous injection.” 2019. Web. 19 Jan 2021.

Vancouver:

Martin M. Characterization of AAVrh.10 as a vector to deliver long-lasting genetic constructs into neurons of neonatal mice following intravenous injection. [Internet] [Masters thesis]. University of Manitoba; 2019. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/1993/34637.

Council of Science Editors:

Martin M. Characterization of AAVrh.10 as a vector to deliver long-lasting genetic constructs into neurons of neonatal mice following intravenous injection. [Masters Thesis]. University of Manitoba; 2019. Available from: http://hdl.handle.net/1993/34637

15. Bender, Heather Rose. Crossing the blood-brain barrier: siRNA treatment for prion diseases.

Degree: PhD, Microbiology, Immunology, and Pathology, 2017, Colorado State University

URL: http://hdl.handle.net/10217/185705

► Protein misfolding diseases such as prion diseases, Alzheimer's disease, and Parkinson's disease, are fatal neurodegenerative diseases caused by a misfolded protein. There are no known… (more)

▼ Protein misfolding diseases such as prion diseases, Alzheimer's disease, and Parkinson's disease, are fatal neurodegenerative diseases caused by a misfolded protein. There are no known therapeutics that extend survival times of afflicted individuals with these diseases. An attractive therapeutic option for protein misfolding disorder is RNA interference, which uses either short hairpin RNA or small interfering RNA (siRNA) to target a specific mRNA for degradation that results in a reduction of protein levels. The reduction of a target mRNA/protein can result in a decrease of misfolded protein in the central nervous system (CNS). However, crossing the blood-brain barrier remains the main challenge for developing RNA interference therapeutics to the CNS. Liposomes are commonly utilized to deliver siRNA to peripheral sites and are being investigated for their ability to deliver siRNA to the brain. We have previously reported on a new liposome delivery system that delivered siRNA targeted towards the cellular prion protein, PrPC, to mouse neuroblastoma cells. PrPC is a normal host cellular protein that misfolds into a protease resistant isomer, PrPRes, which leads to the development of prion diseases. We call these siRNA delivery vehicles: liposome-siRNA-peptide complexes (LSPCs). LSPCs are targeted towards the CNS using a small peptide from the rabies virus glycoprotein, called RVG-9r. In the second chapter of this dissertation, we show that an intravenous injection of LSPCs results in a 40-50% reduction of neuronal PrPC. Upon injection of LSPCs, we observed that half of all treated mice had PrPC siRNA targeted towards the area of the brain several hours after injection. However, we also observed a clearance of PrPC siRNA by the kidneys in the other half of LSPCs-treated mice. Therefore, we designed two other liposomal delivery vehicles that would allow us to encapsulate the siRNA in the liposome and covalently link RVG-9r to the outside of the liposome. We also added PEG lipids to these new delivery vehicles to extend the circulation half-life of the liposomes. We call these additional delivery vehicles peptide-addressed liposome-encapsulated therapeutic siRNA (PALETS). The two PALETS formulations include one cationic (DOTAP [1,2-dioleoyl-3-trimethylammonium-propane]) PALETS and one anionic (DSPE [1,2-Distearoyl-sn-glycero-3-phosphoethanolamine]) PALETS. We have utilized the cation protamine sulfate to encapsulate the siRNA within the anionic PALETS. The addition of protamine sulfate to the siRNA resulted in an encapsulation efficiency of 80-90% in DSPE PALETS. Four days after treatment with LSPCs and PALETS, LSPCs have the biggest decrease in neuronal PrPC on the cellular surface, while DOTAP PALETS have the greatest reduction of PrPC-positive cells. DSPE PALETS showed no statistical difference between the treated and untreated mice at this time point; however, two of the three treated mice did have a decrease in their neuronal PrPC, indicating that this delivery vehicle is able to deliver PrPC siRNA to the brain.… Advisors/Committee Members: Zabel, Mark (advisor), Telling, Glenn (committee member), Gustafson, Daniel (committee member), Bamburg, James (committee member), Dow, Steve (committee member).

Subjects/Keywords: prions; siRNA; PrPC; blood brain barrier

13 more images…

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APA (6^th Edition):

Bender, H. R. (2017). Crossing the blood-brain barrier: siRNA treatment for prion diseases. (Doctoral Dissertation). Colorado State University. Retrieved from http://hdl.handle.net/10217/185705

Chicago Manual of Style (16^th Edition):

Bender, Heather Rose. “Crossing the blood-brain barrier: siRNA treatment for prion diseases.” 2017. Doctoral Dissertation, Colorado State University. Accessed January 19, 2021. http://hdl.handle.net/10217/185705.

MLA Handbook (7^th Edition):

Bender, Heather Rose. “Crossing the blood-brain barrier: siRNA treatment for prion diseases.” 2017. Web. 19 Jan 2021.

Vancouver:

Bender HR. Crossing the blood-brain barrier: siRNA treatment for prion diseases. [Internet] [Doctoral dissertation]. Colorado State University; 2017. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/10217/185705.

Council of Science Editors:

Bender HR. Crossing the blood-brain barrier: siRNA treatment for prion diseases. [Doctoral Dissertation]. Colorado State University; 2017. Available from: http://hdl.handle.net/10217/185705

16. Luckgei, Nina. Structural and dynamic features of Sup35 prion fibrils by solid-state NMR spectroscopy : Caractérisation structurale et dynamique des fibrilles du prion Sup35 par spectroscopie RMN du solide.

Degree: Docteur es, Biologie structurale, 2013, Université Claude Bernard – Lyon I

URL: http://www.theses.fr/2013LYO10185

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Les protéines prions sont associées à une classe de maladies neurodégénératives, dont l'encéphalopathie spongiforme transmissible (EST) est la mieux connue. La protéine prion Sup35p représente… (more)

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Les protéines prions sont associées à une classe de maladies neurodégénératives, dont l'encéphalopathie spongiforme transmissible (EST) est la mieux connue. La protéine prion Sup35p représente un tel modèle car elle est non associée à une maladie. Sup35p se compose de trois domaines : un domaine N-terminal qui est responsable de la formation de prion, d'un domaine de milieu (M) qui affiche un degré élevé de flexibilité, et un domaine C-terminal fonctionnel et globulaire. Le fragment Sup35pNM est souvent utilisé comme modèle pour documenter l'assemblage et les propriétés infectieuses de Sup35p. Les études de Sup35p et Sup35pNM par RMN du solide ont révélé d'étonnantes différences structurelles entre les deux cœurs amyloïdes de Sup35p et Sup35pNM. Nos résultats sur Sup35p apportent un nouvel éclairage sur le monde étonnamment diversifié des prions où la variabilité conformationnelle joue un rôle énorme et perturbant. Ils reflètent l'image émergente que les prions sont des unités structurelles complexes. En effet, même s'il affiche une structure très définie, un domaine donné peut adopter des conformations différentes selon les circonstances (en isolation, dans le contexte d'un fragment ou la protéine entière) ou de l'environnement (conditions de tampon, présence de chaperonnes). Nos résultats donnent une explication au niveau moléculaire pour la contractante propension à l'assemblage et l'infectiosité de Sup35pNM et Sup35p, et soulignent l'importance primordiale d'une caractérisation structurale au niveau moléculaire des agrégats utilisés dans des études fonctionnelles

Prion proteins are associated with a class of neurodegenerative diseases, including transmissible spongiform encephalopathy (TSE) which is the best known. The prion protein Sup35p displays a model system because it is not associated with disease. Sup35p consists of three domains: an N-terminal domain which is responsible for the prion formation, a middle domain (M) that displays a high degree of flexibility, and a functional C-terminal domain. Sup35pNM the fragment is often used as a model to document for the assembly and infectious properties of Sup35p. Solid-state NMR studies of Sup35p and Sup35pNM fibrils showed amazing structural differences between the two amyloid cores. Our results shed new light on the surprisingly diverse world of prions where conformational variability plays a huge role. They reflect the emerging picture that prions are complex structural units. Even if it displays a very defined structure, a given field may adopt different conformations depending on the circumstances (in isolation, in the context of the whole protein or fragment) or the environment (buffer conditions, presence of chaperones). Our results provide an explanation at the molecular level for the contrasting propensity assembly and infectivity Sup35pNM and Sup35p, and emphasize the central importance of a structural characterization at the molecular level

Advisors/Committee Members: Böckmann, Anja (thesis director).

Subjects/Keywords: Spectroscopie RMN du solide; Prions; Attribution séquentielle; Solid-state NMR spectroscopy; Prions; Sequential assignment; 572.6

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Luckgei, N. (2013). Structural and dynamic features of Sup35 prion fibrils by solid-state NMR spectroscopy : Caractérisation structurale et dynamique des fibrilles du prion Sup35 par spectroscopie RMN du solide. (Doctoral Dissertation). Université Claude Bernard – Lyon I. Retrieved from http://www.theses.fr/2013LYO10185

Chicago Manual of Style (16^th Edition):

Luckgei, Nina. “Structural and dynamic features of Sup35 prion fibrils by solid-state NMR spectroscopy : Caractérisation structurale et dynamique des fibrilles du prion Sup35 par spectroscopie RMN du solide.” 2013. Doctoral Dissertation, Université Claude Bernard – Lyon I. Accessed January 19, 2021. http://www.theses.fr/2013LYO10185.

MLA Handbook (7^th Edition):

Luckgei, Nina. “Structural and dynamic features of Sup35 prion fibrils by solid-state NMR spectroscopy : Caractérisation structurale et dynamique des fibrilles du prion Sup35 par spectroscopie RMN du solide.” 2013. Web. 19 Jan 2021.

Vancouver:

Luckgei N. Structural and dynamic features of Sup35 prion fibrils by solid-state NMR spectroscopy : Caractérisation structurale et dynamique des fibrilles du prion Sup35 par spectroscopie RMN du solide. [Internet] [Doctoral dissertation]. Université Claude Bernard – Lyon I; 2013. [cited 2021 Jan 19]. Available from: http://www.theses.fr/2013LYO10185.

Council of Science Editors:

Luckgei N. Structural and dynamic features of Sup35 prion fibrils by solid-state NMR spectroscopy : Caractérisation structurale et dynamique des fibrilles du prion Sup35 par spectroscopie RMN du solide. [Doctoral Dissertation]. Université Claude Bernard – Lyon I; 2013. Available from: http://www.theses.fr/2013LYO10185

Université Montpellier II

17. Delmouly, Karine. Cellules Souches Neurales : modélisation et thérapie cellulaire des maladies à prions. : Neural stem Cells : infection modeling and cell therapy of prion diseases.

Degree: Docteur es, Biologie cellulaire, 2010, Université Montpellier II

URL: http://www.theses.fr/2010MON20134

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Les Encéphalopathies Spongiformes Subaigües Transmissibles (ESST) sont des maladies neurodégénératives caractérisées par une longue période d'incubation asymptomatique à l'issue fatale. Elles sont induites par l'accumulation,… (more)

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Les Encéphalopathies Spongiformes Subaigües Transmissibles (ESST) sont des maladies neurodégénératives caractérisées par une longue période d'incubation asymptomatique à l'issue fatale. Elles sont induites par l'accumulation, au niveau du système nerveux central (SNC), de l'isoforme pathogène de la protéine du prion (PrPSc) entraînant une dégénération des cellules neuronales ainsi qu'une astrogliogénèse. La PrPSc, qui joue un rôle central dans la transmission de la maladie, est produite par conversion de la forme physiologique de la protéine du prion (PrPC). Les mécanismes de conversion de la PrPC et de propagation de la PrPSc sont incertains ainsi que les mécanismes moléculaires à la base des maladies à prions. Dans le cadre de la création et l'amélioration de modèles de culture cellulaire, il a été montré que les Cellules Souches Neurales (CSN) issues du SNC permettent la conversion in vitro de la PrPC en PrPSc. Dans cette étude, nous avons utilisé les CSN pour optimiser et caractériser les conditions d'infection des cellules et émis l'hypothèse que la modification des conditions de culture pouvait moduler la production de PrPSc dans les CSN. Pour cela, nous avons ajouté des facteurs influençant l'identité cellulaire dans nos cultures et avons montré qu'ils étaient capables d'augmenter la propagation du prion. Ces modèles nous permettent l'étude des mécanismes moléculaires pouvant être à l'origine de l'infection. En parallèle, nous avons montré que l'ajout d'HEPES dans nos cultures inhibe la production de PrPSc dans les CSN de façon dose-dépendante. Par ailleurs, à ce jour il n'existe aucune thérapie capable de stopper la progression de la maladie chez l'homme. Ainsi, nous avons utilisé les CSN dans le but d'élaborer une approche thérapeutique permettant de distribuer des anticorps au sein du SNC pour stopper la réplication du prion. Ces cellules permettront, de plus, de réparer les zones endommagées du cerveau combinant ainsi thérapie cellulaire et génique.

Transmissible Spongiform Encephalopathies (TSE) are neurodegenerative disorders with long asymptomatic incubation periods and fatal issue. They are induced by accumulation of the pathogen isoform of the prion protein (PrPSc) in the central nervous system (CNS) resulting in neuronal degeneration and astrogliosis. PrPSc, produced by the conversion of the physiological form of the prion protein (PrPC), plays a key role in the disease transmission. The mechanisms underlying the conversion of PrPC and the propagation of PrPSc are uncertain just as the molecular mechanisms giving rise to prion diseases. In the aim of creating or improving cell culture models, it has been shown that CNS Neural Stem Cells (NSC) could support PrPC conversion into PrPSc in vitro. In this project, we used NSC to improve and characterize cellular infection and hypothesized that modification of culture conditions could modulate PrPSc production in NSC. Hence, we used factors known to influence cellular identity in our culture model and showed that higher amount of prions were produced.…

Advisors/Committee Members: Lehmann, Sylvain (thesis director).

Subjects/Keywords: Prions; Cellules Souches Neurales; Approche thérapeutique; Prions; Neura Stem Cell; Cell therapy

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Delmouly, K. (2010). Cellules Souches Neurales : modélisation et thérapie cellulaire des maladies à prions. : Neural stem Cells : infection modeling and cell therapy of prion diseases. (Doctoral Dissertation). Université Montpellier II. Retrieved from http://www.theses.fr/2010MON20134

Chicago Manual of Style (16^th Edition):

Delmouly, Karine. “Cellules Souches Neurales : modélisation et thérapie cellulaire des maladies à prions. : Neural stem Cells : infection modeling and cell therapy of prion diseases.” 2010. Doctoral Dissertation, Université Montpellier II. Accessed January 19, 2021. http://www.theses.fr/2010MON20134.

MLA Handbook (7^th Edition):

Delmouly, Karine. “Cellules Souches Neurales : modélisation et thérapie cellulaire des maladies à prions. : Neural stem Cells : infection modeling and cell therapy of prion diseases.” 2010. Web. 19 Jan 2021.

Vancouver:

Delmouly K. Cellules Souches Neurales : modélisation et thérapie cellulaire des maladies à prions. : Neural stem Cells : infection modeling and cell therapy of prion diseases. [Internet] [Doctoral dissertation]. Université Montpellier II; 2010. [cited 2021 Jan 19]. Available from: http://www.theses.fr/2010MON20134.

Council of Science Editors:

Delmouly K. Cellules Souches Neurales : modélisation et thérapie cellulaire des maladies à prions. : Neural stem Cells : infection modeling and cell therapy of prion diseases. [Doctoral Dissertation]. Université Montpellier II; 2010. Available from: http://www.theses.fr/2010MON20134

18. Wang, Kai. Protéines infectieuses chez la levure Saccharomyces cerevisiae : un mal pour un bien ? Modulation de la propagation de prions de levure par le protéasome et les chaperons moléculaires durant la transition duauxique et la phase stationnaire : Infectious Proteins in the Yeast Saccharomyces Cerevisiae : a Blessing in Disguise ? Modulation of Yeast Prion Propagation by the Proteasome and Molecular Chaperons During Diauxic Shift and Stationary Phase.

Degree: Docteur es, Sciences de la vie et de la santé, 2016, Université Paris-Saclay (ComUE)

URL: http://www.theses.fr/2016SACLS212

► Les prions sont des protéines qui suite à des changements de conformation acquièrent un caractère infectieux. Ils sont à l’origine de traits dominants, héritables de… (more)

▼ Les prions sont des protéines qui suite à des changements de conformation acquièrent un caractère infectieux. Ils sont à l’origine de traits dominants, héritables de façon non-Mendélienne, chez les mammifères, les champignons filamenteux et les levures. Le mauvais repliement et l’agrégation des protéines sont à l’origine de plus de 40 maladies, parmi lesquelles on retrouve des maladies neurodégénératives telles que les maladies d’Alzheimer, de Parkinson et de Huntington. Il a été montré que les formes agrégées des protéines supposées responsables de ces maladies (i.e. peptide amyloïde-β, tau, α-synucléine, huntingtine) se propagent de cellule en cellule à la manière des prions. La levure Saccharomyces cerevisiae possède plusieurs prions qui sont autant d’excellents modèles biologiques pour la compréhension des mécanismes de formation et de propagation des prions.[PSI+] et [URE3], issus respectivement de la conversion sous forme prion du terminateur de la traduction Sup35p et d’un régulateur du métabolisme azoté Ure2p, sont à ce jour les deux prions les mieux documentés chez la levure. Les chaperons moléculaires et leurs co-chaperons modulent la formation, la réplication et la propagation des prions chez la levure. Cependant, l’élimination ou la dégradation de ces prions sont encore mal connus. Notre laboratoire a montré que le protéasome 26S est capable de dégrader les formes soluble et fibrillaire de Sup35p. Dans la première partie de ma thèse, nous avons étudié le rôle du protéasome 26S dans la dégradation des formes soluble et fibrillaire d’Ure2p. Nous avons montré que, comme pour Sup35p, le protéasome 26S dégrade Ure2p soluble en générant des peptides amyloïdes issus du domaine prion N-terminal ainsi qu’un fragment C-terminal résistant à la protéolyse. Nous avons montré que le domaine prion déstructuré est nécessaire pour la reconnaissance et la dégradation par le protéasome. Contrairement à ce qui avait été observé pour Sup35p, Ure2p sous sa forme fibrillaire est totalement résistante à la dégradation protéasomale. Nous suggérons que la variabilité structurale aux seins des particules de prions dans un contexte cellulaire dicte leurs interactions avec les machineries protéolytiques, et plus particulièrement avec le protéasome.Les prions de levure ont principalement été étudiés dans un contexte de cellules en division active. Cependant, dans la nature, la plupart des cellules sont retrouvées dans un état quiescent post-mitotique. Nous n’avons que très peu d’informations sur le devenir des particules de prions lorsque les cellules entrent dans un état quiescent. De même les conséquences physiologiques des prions sur la survie à long terme des levures sont très peu documentées. Dans la seconde partie de ma thèse, nous avons utilisé le prion [PSI+] comme modèle pour répondre à ces questions. Différentes conformations des agrégats de Sup35p conduisent à des souches phénotypiquement distinctes du prion [PSI+]. Nous avons constaté que les agrégats de Sup35p subissent des changements ultra-structuraux et fonctionnels au… Advisors/Committee Members: Kabani, Mehdi (thesis director).

Subjects/Keywords: Prions de levure; Protéasome 26S; Chaperons moléculaires; Yeast prions; 26S Proteasome; Molecular Chaperons

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Wang, K. (2016). Protéines infectieuses chez la levure Saccharomyces cerevisiae : un mal pour un bien ? Modulation de la propagation de prions de levure par le protéasome et les chaperons moléculaires durant la transition duauxique et la phase stationnaire : Infectious Proteins in the Yeast Saccharomyces Cerevisiae : a Blessing in Disguise ? Modulation of Yeast Prion Propagation by the Proteasome and Molecular Chaperons During Diauxic Shift and Stationary Phase. (Doctoral Dissertation). Université Paris-Saclay (ComUE). Retrieved from http://www.theses.fr/2016SACLS212

Chicago Manual of Style (16^th Edition):

Wang, Kai. “Protéines infectieuses chez la levure Saccharomyces cerevisiae : un mal pour un bien ? Modulation de la propagation de prions de levure par le protéasome et les chaperons moléculaires durant la transition duauxique et la phase stationnaire : Infectious Proteins in the Yeast Saccharomyces Cerevisiae : a Blessing in Disguise ? Modulation of Yeast Prion Propagation by the Proteasome and Molecular Chaperons During Diauxic Shift and Stationary Phase.” 2016. Doctoral Dissertation, Université Paris-Saclay (ComUE). Accessed January 19, 2021. http://www.theses.fr/2016SACLS212.

MLA Handbook (7^th Edition):

Wang, Kai. “Protéines infectieuses chez la levure Saccharomyces cerevisiae : un mal pour un bien ? Modulation de la propagation de prions de levure par le protéasome et les chaperons moléculaires durant la transition duauxique et la phase stationnaire : Infectious Proteins in the Yeast Saccharomyces Cerevisiae : a Blessing in Disguise ? Modulation of Yeast Prion Propagation by the Proteasome and Molecular Chaperons During Diauxic Shift and Stationary Phase.” 2016. Web. 19 Jan 2021.

Vancouver:

Wang K. Protéines infectieuses chez la levure Saccharomyces cerevisiae : un mal pour un bien ? Modulation de la propagation de prions de levure par le protéasome et les chaperons moléculaires durant la transition duauxique et la phase stationnaire : Infectious Proteins in the Yeast Saccharomyces Cerevisiae : a Blessing in Disguise ? Modulation of Yeast Prion Propagation by the Proteasome and Molecular Chaperons During Diauxic Shift and Stationary Phase. [Internet] [Doctoral dissertation]. Université Paris-Saclay (ComUE); 2016. [cited 2021 Jan 19]. Available from: http://www.theses.fr/2016SACLS212.

Council of Science Editors:

Wang K. Protéines infectieuses chez la levure Saccharomyces cerevisiae : un mal pour un bien ? Modulation de la propagation de prions de levure par le protéasome et les chaperons moléculaires durant la transition duauxique et la phase stationnaire : Infectious Proteins in the Yeast Saccharomyces Cerevisiae : a Blessing in Disguise ? Modulation of Yeast Prion Propagation by the Proteasome and Molecular Chaperons During Diauxic Shift and Stationary Phase. [Doctoral Dissertation]. Université Paris-Saclay (ComUE); 2016. Available from: http://www.theses.fr/2016SACLS212

INP Toulouse

19. Douet, Jean-Yves. Perméabilité des barrières de transmission et évaluation du risque iatrogène associé aux agents responsables des Encéphalopathies Spongiformes Transmissibles : Permeability of transmission barriers and evaluation of the iatrogenic risk associated with Transmissible Spongiform Encephalopathies.

Degree: Docteur es, Pathologie, Toxicologie, Génétique et Nutrition, 2015, INP Toulouse

URL: http://www.theses.fr/2015INPT0033

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Les Encéphalopathies Spongiformes transmissibles (EST) sont des maladies neurodégénératives fatales caractérisées par l’accumulation d’un conformère anormal (PrPSc) d’une protéine de l’hôte (PrP). Chez l’homme, plusieurs… (more)

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Les Encéphalopathies Spongiformes transmissibles (EST) sont des maladies neurodégénératives fatales caractérisées par l’accumulation d’un conformère anormal (PrPSc) d’une protéine de l’hôte (PrP). Chez l’homme, plusieurs centaines de cas de transmissions iatrogènes de la maladie de Creutzfeldt Jakob (MCJ) ont été identifiées, notamment chez des patients ayant fait l’objetd’ une greffe de dure-mère, de cornée ou des injections d’hormones de croissance extractives. Plus récemment, plusieurs cas du variant de la maladie de Creutzfeldt Jakob (vMCJ) ont été observés chez des patients transfusés avec des produits sanguins issus de donneurs en incubation de la maladie. D’un point de vue sanitaire, l’évaluation du risque de contamination interindividuelle par des tissus ou des fluides biologiques issus de patients atteints représente un enjeu important en matière de santé publique. La première partie de notre travail a consisté à comparer la sensibilité relative de modèles de souris transgéniques sur-exprimant la PrP à celle de l’hôte conventionnel exprimant la même séquence. Les résultats obtenus ont validé le concept d’une absence d’impact du niveau d’expression de la PrP ou du fond génétique de l’hôte sur la sensibilité finale du modèle à l’infection. A l’aide de ces modèles de souris transgéniques, nous avons alors mesuré les niveaux d’infectiosité dans le sang de patients atteints de différentes formes d’’EST. Chez un patient atteint de vMCJ, nous avons mis en évidence de faibles niveaux d’infectiosité dans les concentrés de globules rouges, les leucocytes et le plasma. Nous avons également pu détecter de l’infectiosité dans le plasma issu de 2 patients atteints de sMCJ sur 4 testés. Parallèlement à ces expériences, nous avons démontré dans un modèle expérimental d’infection chez le mouton, que l’administration de 104 à 105 leucocytes suffisent à transmettre par voire transfusionnelle la maladie. Ces résultats soulignent l’intérêt et les limites de la leuco-déplétion appliquée de manière standard en médicine transfusionnelle, pour limiter les risques de transmission du vMCJ. Enfin, nous avons testé la capacité de différents outils in vitro à détecter la présence des Prions dans le sang.

Transmissible spongiform encephalopathies (TSE) are fatal neurodegenerative disorders occurring in a wide spectrum of animals. They are characterized by accumulation of abnormally folded conformers (PrPSc) derived from normal cellular PrP protein (PrP) of the host. In human, many iatrogenic transmissions of Creutzfeldt Jakob disease (CJD) have been reported after dura mater graft, corneal graft or extractive growth hormone injections, prepared from affected donors. More recently, several cases of vCJD transmissions were reported in individuals that were transfused with blood from asymptomatic donors that subsequently developed vCJD. Risk assessment of interindividual transmission with contaminated tissues or body fluids remains a major public health issue. In a first part, we validated the final pertinence of infectious titers as…

Advisors/Committee Members: Andréoletti, Olivier (thesis director), Lacroux, Caroline (thesis director).

Subjects/Keywords: Prions; Est; Maladie de Creutzfeldt-Jakob; Transfusion sanguine; Prions; Tse; Creutzfeldt-Jakob disease; Blood transfusion

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Douet, J. (2015). Perméabilité des barrières de transmission et évaluation du risque iatrogène associé aux agents responsables des Encéphalopathies Spongiformes Transmissibles : Permeability of transmission barriers and evaluation of the iatrogenic risk associated with Transmissible Spongiform Encephalopathies. (Doctoral Dissertation). INP Toulouse. Retrieved from http://www.theses.fr/2015INPT0033

Chicago Manual of Style (16^th Edition):

Douet, Jean-Yves. “Perméabilité des barrières de transmission et évaluation du risque iatrogène associé aux agents responsables des Encéphalopathies Spongiformes Transmissibles : Permeability of transmission barriers and evaluation of the iatrogenic risk associated with Transmissible Spongiform Encephalopathies.” 2015. Doctoral Dissertation, INP Toulouse. Accessed January 19, 2021. http://www.theses.fr/2015INPT0033.

MLA Handbook (7^th Edition):

Douet, Jean-Yves. “Perméabilité des barrières de transmission et évaluation du risque iatrogène associé aux agents responsables des Encéphalopathies Spongiformes Transmissibles : Permeability of transmission barriers and evaluation of the iatrogenic risk associated with Transmissible Spongiform Encephalopathies.” 2015. Web. 19 Jan 2021.

Vancouver:

Douet J. Perméabilité des barrières de transmission et évaluation du risque iatrogène associé aux agents responsables des Encéphalopathies Spongiformes Transmissibles : Permeability of transmission barriers and evaluation of the iatrogenic risk associated with Transmissible Spongiform Encephalopathies. [Internet] [Doctoral dissertation]. INP Toulouse; 2015. [cited 2021 Jan 19]. Available from: http://www.theses.fr/2015INPT0033.

Council of Science Editors:

Douet J. Perméabilité des barrières de transmission et évaluation du risque iatrogène associé aux agents responsables des Encéphalopathies Spongiformes Transmissibles : Permeability of transmission barriers and evaluation of the iatrogenic risk associated with Transmissible Spongiform Encephalopathies. [Doctoral Dissertation]. INP Toulouse; 2015. Available from: http://www.theses.fr/2015INPT0033

Université Paris-Sud – Paris XI

20. Hernandez-Rapp, Julia. Rôle de la protéine prion dans les neurones : de la physiologie à la pathologie : Role of the Prion Protein in Neurons : From Physiology to Pathology.

Degree: Docteur es, Biologie cellulaire, 2013, Université Paris-Sud – Paris XI

URL: http://www.theses.fr/2013PA11T073

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La conversion de la protéine prion cellulaire (PrPC) en protéine prion scrapie (PrPSc) est à l’origine des encéphalopathies spongiformes transmissibles (EST). La toxicité de la… (more)

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La conversion de la protéine prion cellulaire (PrPC) en protéine prion scrapie (PrPSc) est à l’origine des encéphalopathies spongiformes transmissibles (EST). La toxicité de la PrPSc est restreinte aux neurones et implique la déviation de la (des) fonction(s) de la PrPC. Une action neurospécifique de la PrPC est le recrutement de la src kinase Fyn. Dans ce travail, nous montrons que la PrPC est capable de mobiliser une autre src kinase, Lyn, via la cavéoline (cav) dans les neurones. Une cible du couplage PrPC-cav-Lyn, restreint aux corps cellulaires, est la kinase GSK3ß. L’inactivation de GSK3ß par la PrPC intervient dans la régulation des fonctions neuronales, en limitant l’activité du récepteur sérotoninergique 1B. D’autre part, nous montrons que dans les cellules infectées par les prions, l’accumulation de PrPSc induit le recrutement constitutif de la plateforme PrPC-cav-Fyn, à l’origine d’un stress oxydant. Ce gain de fonction entraine notamment un défaut de clivage par la metalloprotéase MMP-9, dont une des conséquences est l’accumulation du peptide Aß. Un autre impact de l’infection est la suractivation de la kinase PDK1, qui génère une perte de fonction de la metalloprotéase TACE. Dans des neurones « Alzheimer », on observe également cette cascade délétère, qui dépend de la PrPC. L’inhibition de PDK1 dans des modèles d’infection par les prions ou de maladie d’Alzheimer permet de rétablir l’activité d’alpha-clivage de TACE vis-à-vis de ses substrats, la PrPC, APP et le récepteur au TNF-alpha. L’effet bénéfique observé in vivo permet de définir PDK1 comme une cible thérapeutique potentielle pour les EST et la maladie d’Alzheimer. En résumé, ce travail illustre comment une meilleure connaissance de la fonction de signalisation de la PrPC peut permettre de progresser dans la compréhension des mécanismes de neurodégénérescence associés non seulement aux maladies à prions, mais également à la maladie d’Alzheimer.

Transmissible spongiform encephalopathies (TSE) are characterized by the conversion of the cellular prion protein (PrPC) into its scrapie isoform (PrPSc). PrPSc-mediated toxicity is restricted to neurons and results from the subversion of PrPC function(s). Some neuronal specificity of PrPC signaling relates to its coupling to the Fyn src kinase. In this work, we report that PrPC has the capacity to mobilize another src kinase, Lyn, via caveolin in neurons. A downstream effector of the PrPC-cav-Lyn signaling complex, which is spatially restricted to cell bodies, is the GSK3ß kinase. The inactivation of GSK3ß by PrPC takes part to the control of neuronal functions by negatively regulating the activity of the serotonin 1B receptor. Furthermore, we show that in prion-infected cells, PrPSc constitutively activates the PrPC-cav-Fyn platform, leading to oxidative-stress conditions. This toxic gain of PrPC function induces a defect in metalloproteinase MMP-9 activity, leading to increased Aß levels. Another impact of prion infection is the overactivation of the PDK1 kinase, which results in the loss of function…

Advisors/Committee Members: Mouillet-Richard, Sophie (thesis director).

Subjects/Keywords: Prions; Signalisation; Peptide Aß; Maladies neurodégénératives; Prions; Signaling; Aß Peptide; Neurodegeneratives diseases

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Hernandez-Rapp, J. (2013). Rôle de la protéine prion dans les neurones : de la physiologie à la pathologie : Role of the Prion Protein in Neurons : From Physiology to Pathology. (Doctoral Dissertation). Université Paris-Sud – Paris XI. Retrieved from http://www.theses.fr/2013PA11T073

Chicago Manual of Style (16^th Edition):

Hernandez-Rapp, Julia. “Rôle de la protéine prion dans les neurones : de la physiologie à la pathologie : Role of the Prion Protein in Neurons : From Physiology to Pathology.” 2013. Doctoral Dissertation, Université Paris-Sud – Paris XI. Accessed January 19, 2021. http://www.theses.fr/2013PA11T073.

MLA Handbook (7^th Edition):

Hernandez-Rapp, Julia. “Rôle de la protéine prion dans les neurones : de la physiologie à la pathologie : Role of the Prion Protein in Neurons : From Physiology to Pathology.” 2013. Web. 19 Jan 2021.

Vancouver:

Hernandez-Rapp J. Rôle de la protéine prion dans les neurones : de la physiologie à la pathologie : Role of the Prion Protein in Neurons : From Physiology to Pathology. [Internet] [Doctoral dissertation]. Université Paris-Sud – Paris XI; 2013. [cited 2021 Jan 19]. Available from: http://www.theses.fr/2013PA11T073.

Council of Science Editors:

Hernandez-Rapp J. Rôle de la protéine prion dans les neurones : de la physiologie à la pathologie : Role of the Prion Protein in Neurons : From Physiology to Pathology. [Doctoral Dissertation]. Université Paris-Sud – Paris XI; 2013. Available from: http://www.theses.fr/2013PA11T073

21. Bohl, Jan. Characterisation of non-covalent PrP assemblies : Caractérisation des assemblages non-covalents de PrP.

Degree: Docteur es, Chimie, 2019, Université Paris-Saclay (ComUE)

URL: http://www.theses.fr/2019SACLS284

► L’étude de l’interaction entre des protéines et leurs ligands est essentielle pour la compréhension de leur rôle physiologique ainsi que de leur rôle dans la… (more)

▼ L’étude de l’interaction entre des protéines et leurs ligands est essentielle pour la compréhension de leur rôle physiologique ainsi que de leur rôle dans la mise en place de pathologies. En particulier, dans le cas de maladies neurodégénératives, comme les maladies d’Alzheimer ou de Creutzfeld-Jacob, ou d’autres pathologies liées au mépliement de protéines, la compréhension des interactions entre protéines, qui peuvent modifier de façon considérable le paysage conformationnel des partenaires, est une des clés pour décrypter les étapes moléculaires élémentaires induisant une cascade d’événements qui mènent à la formation d’assemblages protéiques de grande taille. Dans le cadre de cette thèse, nous avons étudié la dynamique de taille de trois types d’assemblages protéines/ peptides.Interactions faibles impliquées dans la structuration d’assemblages de PrPSc et dans l’équilibre entre les formes PrPSc et suPrP : Dans un premier temps, l’étude des étapes précoces de la réplication du prion nous a permis de mettre en évidence une voie de diversification structurale qui implique une voie de templating secondaire. En utilisant une méthode de solubilisation en conditions natives et une approche reposant sur une série de souches différentes, nous avons démontré que, pour toutes les souches testées, les assemblages de prion ont la propriété de se dépolymériser en deux ensembles discrets d’assemblages oligomériques, dont la taille varie entre des dimères et tétramères. Des approches d’amplification de prion in vitro et in vivo ont démontré que ces assemblages oligomériques comportent toute l’information nécessaire à la réplication ainsi que les déterminants structuraux de la souche. Le motif de glycosylation, la cartographie par épitopes ainsi que l’empreinte PK ont mis en évidence des différences structurales entre les espèces oligomériques, soulignant la coexistence d’ensembles d’assemblages structuralement distincts au sein d’une souche donnée. Des expériences de dépliement partiel ont montré la présence d’une dynamique constitutionnelle entre les assemblages reposant sur un échange de matière et un réarrangement structurel à l’échelle de l’unité élémentaire (suPrP) ainsi qu’une diversité structurale au sein des assemblages de prion.Partenaires et oxydation de la PrPc: Bien que des travaux préalables aient mis en évidence l’existence d’interactions entre PrP et Aβ, Aβ1-40 ne forme que des complexes très instables avec la PrP monomérique. La spectrométrie de masse n’a pas permis de mettre en évidence cette interaction, même après optimisation des paramètres en conditions natives ou via des mesures indirectes reposant sur des échanges hydrogène - deutérium d’amide. L’oxydation radioloytique de la PrPC a été étudiée par SEC couplée à la mobilité ionique et la spectrométrie de masse, montrant la formation d’assemblages de haut poids moléculaires associée à des changements de structure.Fortes interactions peptide/peptide : Le système Synapt G2Si (Waters), qui combine de la mobilité ionique avec de la spectrométrie de masse, a été… Advisors/Committee Members: Van der Rest, Guillaume (thesis director).

Subjects/Keywords: Complexes peptidiques; Assemblages de protéines; Abeta; Oxydation; Spectrométrie de masse; Prions; Peptide complexes; Protein assemblies; Abeta; Oxidation; Mass spectrometry; Prions

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Bohl, J. (2019). Characterisation of non-covalent PrP assemblies : Caractérisation des assemblages non-covalents de PrP. (Doctoral Dissertation). Université Paris-Saclay (ComUE). Retrieved from http://www.theses.fr/2019SACLS284

Chicago Manual of Style (16^th Edition):

Bohl, Jan. “Characterisation of non-covalent PrP assemblies : Caractérisation des assemblages non-covalents de PrP.” 2019. Doctoral Dissertation, Université Paris-Saclay (ComUE). Accessed January 19, 2021. http://www.theses.fr/2019SACLS284.

MLA Handbook (7^th Edition):

Bohl, Jan. “Characterisation of non-covalent PrP assemblies : Caractérisation des assemblages non-covalents de PrP.” 2019. Web. 19 Jan 2021.

Vancouver:

Bohl J. Characterisation of non-covalent PrP assemblies : Caractérisation des assemblages non-covalents de PrP. [Internet] [Doctoral dissertation]. Université Paris-Saclay (ComUE); 2019. [cited 2021 Jan 19]. Available from: http://www.theses.fr/2019SACLS284.

Council of Science Editors:

Bohl J. Characterisation of non-covalent PrP assemblies : Caractérisation des assemblages non-covalents de PrP. [Doctoral Dissertation]. Université Paris-Saclay (ComUE); 2019. Available from: http://www.theses.fr/2019SACLS284

Universitat de Barcelona

22. Urrea Zazurca, Laura. Funciones de la proteína priónica celular, alfa-sinucleína y reelina en enfermedades neurodegenerativas.

Degree: Departament de Biologia Cel·lular, Fisiologia i Immunologia, 2018, Universitat de Barcelona

URL: http://hdl.handle.net/10803/482168

► Many neurodegenerative diseases are characterized by the loss of neurons and intracellular accumulation of abnormal proteins, with the formation of inclusion bodies. Parkinson’s disease (PD)… (more)

▼ Many neurodegenerative diseases are characterized by the loss of neurons and intracellular accumulation of abnormal proteins, with the formation of inclusion bodies. Parkinson’s disease (PD) is the second most common form of neurodegenerative diseases. PD shows an abnormal accumulation of α-synuclein aggregates in neurons, called Lewy bodies (LB). Several groups have reported that abnormal form of α-synuclein can propagate through the cells and, consequently, form inclusions. Thus, it has been suggested different molecular mechanisms involved in α-synuclein propagation. It has been reported that cellular prion protein (PrPc) is a receptor of β-amyloid. In this study, we analyse whether the PrPc is a receptor for α-synuclein. Animals with different PrPc expression were intracranially injected with α-synuclein protofibrils. We observe that PrPc expression is not mandatory for α-synuclein propagation, but PrPc-overexpressing mice show more aggregates than in PrPc absence. Moreover, charge cluster domain of PrPc is essential for α-synuclein binding. In addition, we study Reelin levels in different neurodegenerative diseases. Reelin is a glycoprotein that is crucial for the correct cytoarchitectonic organization of the developing Central Nervous System. Decreased levels of Reelin lead to synaptic dysfunction or neurodegeneration. In the present study, we analyse the changes in Reelin and Reln mRNA in Alzheimer’s disease, Dementia with Lewy Bodies (DLB), Parkinson´s disease (PD) and sporadic Creutzfeldt-Jakob disease (sCJD). Meanwhile, inmunoblot results indicate decreased levels of Reelin in AD and DLB, PD do not show changes. In contrast, it has been detected an increase in sCJD(I). Reelin increased levels depends on reactive oxygen species (ROS). Using inhibitors of ROS production, as DPI and NAC, Reelin levels are maintained. Advisors/Committee Members: [email protected] (authoremail), false (authoremailshow), Río Fernández, José Antonio del (director), Río Fernández, José Antonio del (tutor), true (authorsendemail).

Subjects/Keywords: Malalties neurodegeneratives; Enfermedades neurodegeneratives; Neurodegenerative Diseases; Malalties per prions; Enfermedades por priones; Prion diseases; Prions; Priones; Ciències Experimentals i Matemàtiques; 576

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Urrea Zazurca, L. (2018). Funciones de la proteína priónica celular, alfa-sinucleína y reelina en enfermedades neurodegenerativas. (Thesis). Universitat de Barcelona. Retrieved from http://hdl.handle.net/10803/482168

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Urrea Zazurca, Laura. “Funciones de la proteína priónica celular, alfa-sinucleína y reelina en enfermedades neurodegenerativas.” 2018. Thesis, Universitat de Barcelona. Accessed January 19, 2021. http://hdl.handle.net/10803/482168.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Urrea Zazurca, Laura. “Funciones de la proteína priónica celular, alfa-sinucleína y reelina en enfermedades neurodegenerativas.” 2018. Web. 19 Jan 2021.

Vancouver:

Urrea Zazurca L. Funciones de la proteína priónica celular, alfa-sinucleína y reelina en enfermedades neurodegenerativas. [Internet] [Thesis]. Universitat de Barcelona; 2018. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/10803/482168.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Urrea Zazurca L. Funciones de la proteína priónica celular, alfa-sinucleína y reelina en enfermedades neurodegenerativas. [Thesis]. Universitat de Barcelona; 2018. Available from: http://hdl.handle.net/10803/482168

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

23. Peckeu, Laurène. Physiopathologie des formes infectieuses de maladies à prions humaines : étude des formes iatrogènes secondaires à un traitement par l'hormone de croissance : Physiopathology of the infectious forms of human prion diseases : a study of iatrogenic forms after human cadaver-sourced growth hormone treatment in France.

Degree: Docteur es, Physiologie, physiopathologie et thérapeutique, 2017, Université Pierre et Marie Curie – Paris VI

URL: http://www.theses.fr/2017PA066583

►

Les maladies à prions sont des maladies neurodégénératives et transmissibles. Elles sont à l'origine de formes infectieuses comme la maladie de Creutzfeldt-Jakob iatrogène secondaire à… (more)

▼

Les maladies à prions sont des maladies neurodégénératives et transmissibles. Elles sont à l'origine de formes infectieuses comme la maladie de Creutzfeldt-Jakob iatrogène secondaire à un traitement par hormone de croissance d'origine humaine (MCJ post-hGH). La compréhension des facteurs gouvernant la physiopathologie de ces formes demeure parcellaire. Notre objectif a été de les étudier en analysant la cohorte des patients français exposés à l'hGH. Les analyses épidémiologiques, ont montré, à partir de données quantifiées, pour la première fois chez l'homme, une relation entre la dose d'exposition et le risque de développer la maladie d'une part et la durée de la période d'incubation d'autre part. La modélisation de la période d'incubation, a permis d'estimer que 95% des cas sont déjà apparus et d'évaluer l'influence du polymorphisme au codon 129 du gène codant la protéine prion sur la période d'incubation. L'étude descriptive a montré des similarités clinico-pathologiques entre tous les cas de maladies à prion humaines par contamination périphérique laissant supposer un rôle important de la voie d'exposition. Les expériences de transmission à la souris transgénique devraient permettre de valider les hypothèses que nous avons émises sur l'identité des souches présentes dans les lots contaminés. Ce travail a donc permis de mieux caractériser les facteurs impliqués dans la transmission des maladies à prions chez l'homme et de fournir un cadre méthodologique et des informations qui pourraient être utiles pour évaluer le risque de transmission potentielle des autres protéinopathies du système nerveux central pour lesquelles un mécanisme " prion like " a été proposé.

Prion diseases are fatal and transmissible neurodegenerative disorders. Infectious forms include iatrogenic Creutzfeldt-Jakob disease after human cadaver-sourced growth hormone treatment (hGH-iCJD). Our understanding of the factors governing the pathophysiology of infection, upon exposure to an exogenous prion, remains very limited in humans. The aim of this study was to better understand these phenomena using data from the French cohort of patients who were exposed to this at risk treatment. Using Cox hazards model, we provided the first epidemiological evidence of a relationship between dose of exposure and disease occurrence on one hand and incubation time on the other hand. Incubation period modelling by Weibull distribution estimated that 95% of the cases have already occurred. In a descriptive study, we showed that clinical and neuropathological features resembled other forms of infectious prion diseases after a peripheral contamination supporting a major role of the route of exposure. We also performed experimental transmission to transgenic mice expressing human PrP to test our hypotheses about the infecting prion strain that were transmitted to French hGH-iCJD patients. To conclude, we identified factors implicated in human prion transmission and provided a methodological frame and useful information that could help to evaluate the transmission…

Advisors/Committee Members: Haïk, Stéphane (thesis director), Costagliola, Dominique (thesis director), Brandel, Jean-Philippe (thesis director).

Subjects/Keywords: Epidémiologie; Maladie de Creutzfeldt-Jakob iatrogène; Prions; Souches; Hormone de croissance; Physiopathologie; Iatrogenic Creutzfeldt-Jakob disease; Human growth hormone; Prions; 614.4

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Peckeu, L. (2017). Physiopathologie des formes infectieuses de maladies à prions humaines : étude des formes iatrogènes secondaires à un traitement par l'hormone de croissance : Physiopathology of the infectious forms of human prion diseases : a study of iatrogenic forms after human cadaver-sourced growth hormone treatment in France. (Doctoral Dissertation). Université Pierre et Marie Curie – Paris VI. Retrieved from http://www.theses.fr/2017PA066583

Chicago Manual of Style (16^th Edition):

Peckeu, Laurène. “Physiopathologie des formes infectieuses de maladies à prions humaines : étude des formes iatrogènes secondaires à un traitement par l'hormone de croissance : Physiopathology of the infectious forms of human prion diseases : a study of iatrogenic forms after human cadaver-sourced growth hormone treatment in France.” 2017. Doctoral Dissertation, Université Pierre et Marie Curie – Paris VI. Accessed January 19, 2021. http://www.theses.fr/2017PA066583.

MLA Handbook (7^th Edition):

Peckeu, Laurène. “Physiopathologie des formes infectieuses de maladies à prions humaines : étude des formes iatrogènes secondaires à un traitement par l'hormone de croissance : Physiopathology of the infectious forms of human prion diseases : a study of iatrogenic forms after human cadaver-sourced growth hormone treatment in France.” 2017. Web. 19 Jan 2021.

Vancouver:

Peckeu L. Physiopathologie des formes infectieuses de maladies à prions humaines : étude des formes iatrogènes secondaires à un traitement par l'hormone de croissance : Physiopathology of the infectious forms of human prion diseases : a study of iatrogenic forms after human cadaver-sourced growth hormone treatment in France. [Internet] [Doctoral dissertation]. Université Pierre et Marie Curie – Paris VI; 2017. [cited 2021 Jan 19]. Available from: http://www.theses.fr/2017PA066583.

Council of Science Editors:

Peckeu L. Physiopathologie des formes infectieuses de maladies à prions humaines : étude des formes iatrogènes secondaires à un traitement par l'hormone de croissance : Physiopathology of the infectious forms of human prion diseases : a study of iatrogenic forms after human cadaver-sourced growth hormone treatment in France. [Doctoral Dissertation]. Université Pierre et Marie Curie – Paris VI; 2017. Available from: http://www.theses.fr/2017PA066583

24. Ana Cristina Ribeiro Magalhaes. Internalização e tráfego de PrPs.

Degree: 2005, Universidade Federal de Minas Gerais

URL: http://hdl.handle.net/1843/SMOC-6XLP4M

► A proteína prion celular (PrPsen ou PrPc) é uma proteína expressa em vários tipos celulares, especialmente em neurônios. Esta proteína apresenta uma estrutura rica em… (more)

▼ A proteína prion celular (PrPsen ou PrPc) é uma proteína expressa em vários tipos celulares, especialmente em neurônios. Esta proteína apresenta uma estrutura rica em alfa hélices, no entanto pode sofrer uma mudança de conformação secundária gerando uma isoforma conhecida como PrPres (ou PrPsc). Esta isoforma apresenta uma estrutura predominante de folhas beta e adquire a capacidade de se associar formando amilóides, bem como resistência a tratamento com proteases. Através de um mecanismo biológico ainda pouco esclarecido, PrPres é capaz de promover a conversão de moléculas de PrPsen para PrPres. A formação e deposição de agregados insolúveis de PrPres no sistema nervoso estão relacionados a uma série de doenças neurodegenerativas raras e fatais. A internalização e tráfego intracelular destas isoformas podem revelar informações importantes sobre o papel fisiológico de PrPsen, bem como os mecanismos de infecção e propagação de PrPres entre células. Interessados nestes mecanismos, nosso grupo construiu uma versão da proteína prion celular ligada a green fluorescent protein (GFP) para monitorarmos a distribuição, endocitose e tráfego desta proteína em células neuronais SN56 vivas. Células SN56 expressando esta proteína de fusão (GFP-PrPc) apresentaram a fluorescência distribuída pela membrana plasmática e em compartimentos intracelulares próximos ao núcleo, de maneira similar a proteína endógena. GFP-PrPc foi internalizada e direcionada para uma região perinuclear na presença de cobre, indicando um papel importante deste íon na fisiologia de PrPc. Um mutante de deleção N-terminal (aminoácidos 32 a 121) ligado a GFP apresentou maior acúmulo na membrana plasmática e menor concentração na região perinuclear, sugerindo uma deficiência na endocitose. Além disso, o cobre não foi capaz de induzir a endocitose deste mutante, indicando que a região N-terminal é importante para a endocitose constitutiva e induzida por cobre de PrPc. Experimentos de dupla marcação indicaram que a região perinuclear positiva para GFP-PrPc era constituída de endossomas de reciclagem e Golgi. O mecanismo de endocitose de GFP-PrPc também foi avaliado e a endocitose constitutiva e induzida por cobre de GFP-PrPc foi dependente de dinamina I. Células expressando o fragmento C terminal da proteína AP180, que compete com a proteína endógena responsável pelo recrutamento de clatrina para a membrana plasmática, xiv apresentam 75% de inibição da endocitose dependente de clatrina. Nestas células, a endocitose constitutiva de GFP-PrPc não sofreu alteração e a induzida por cobre apresentou uma inibição parcial, sugerindo que o mecanismo de endocitose de GFPPrPc é complexo, podendo envolver tanto um mecanismo dependente como independente de clatrina. Provavelmente, o mecanismo independente não envolve caveolae, já que não pudemos detectar caveolina, um marcador para caveolae, em células SN56. Nós também avaliamos a internalização e tráfego de PrPres usando diferentes cepas de PrPres conjugadas à molécula fluorescente alexa568. Células SN56 foram capazes de… Advisors/Committee Members: Marco Antonio Maximo Prado, Luiz Armando Cunha De Marco, WALDEREZ ORNELAS DUTRA, VILMA REGINA MARTINS, RAFAEL LINDEN, Marco Antonio Maximo Prado.

Subjects/Keywords: Prions Teses; Proteínas Teses.; Endocitose Teses; Doenças de príon Teses

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Magalhaes, A. C. R. (2005). Internalização e tráfego de PrPs. (Thesis). Universidade Federal de Minas Gerais. Retrieved from http://hdl.handle.net/1843/SMOC-6XLP4M

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Magalhaes, Ana Cristina Ribeiro. “Internalização e tráfego de PrPs.” 2005. Thesis, Universidade Federal de Minas Gerais. Accessed January 19, 2021. http://hdl.handle.net/1843/SMOC-6XLP4M.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Magalhaes, Ana Cristina Ribeiro. “Internalização e tráfego de PrPs.” 2005. Web. 19 Jan 2021.

Vancouver:

Magalhaes ACR. Internalização e tráfego de PrPs. [Internet] [Thesis]. Universidade Federal de Minas Gerais; 2005. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/1843/SMOC-6XLP4M.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Magalhaes ACR. Internalização e tráfego de PrPs. [Thesis]. Universidade Federal de Minas Gerais; 2005. Available from: http://hdl.handle.net/1843/SMOC-6XLP4M

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Manchester

25. Speldewinde, Shaun Harold. Prions, autophagy, ageing and actin cytoskeleton in yeast.

Degree: 2017, University of Manchester

URL: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:308633

► Prions are infectious protein entities capable of self-replication. Prions are the causal agents behind the transmissible spongiform encephalopathies causing neurodegeneration and death in affected organisms.… (more)

▼ Prions are infectious protein entities capable of self-replication. Prions are the causal agents behind the transmissible spongiform encephalopathies causing neurodegeneration and death in affected organisms. Prions have been identified in yeast with the best-characterized prions being [PSI+] and [PIN+], whose respective native proteins are the Sup35 translation termination factor and Rnq1 (function unknown). Autophagy is a cellular housekeeping mechanism mediating the degradation of damaged proteins and superfluous organelles. It is a highly sequential process regulated by autophagy related genes (ATGs). Autophagy has also been implicated in the clearance of amyloidogenic proteins including prions. However, the mechanistic basis underlying this activity is poorly understood, and a key objective of this project was to characterize how autophagy prevents spontaneous prion formation. Our study found that the deletion of core ATGs correlated with an increase in de novo [PSI+] and [PIN+] formation as well as Sup35 aggregation. Enhancement of autophagic flux through spermidine treatment attenuated the increased levels of de novo [PSI+] formation in mutants that normally show elevated levels of [PSI+] formation. Defective autophagy correlated with increased oxidatively damaged Sup35 in an atg1 mutant whereas anaerobic growth abrogated the increased [PSI+] formation in the atg1 mutant to wild-type levels. Our data suggest that autophagy serves a protective role in the clearance of oxidatively damaged Sup35 proteins that otherwise has a higher propensity towards [PSI+] prion formation. We also investigated the role of prion formation and autophagy during yeast chronological ageing which is the time that non-dividing cells remain viable. Prion diseases are associated with advanced age which correlates with a decline in cellular protective mechanisms including autophagy. Our study found an age dependent increase in the frequency of de novo [PSI+] formation with chronological age of yeast cells, more so in an atg1 mutant relative to the wild-type. Autophagy competent cells carrying the [PSI+] and [PIN+] prions also had improved chronological lifespan relative to prion free cells and atg1 cells. Cells carrying the [PSI+] prion elicited elevated autophagic flux that may promote improved lifespan thus suggesting a beneficial role of the [PSI+] prion during chronological ageing. The actin cytoskeleton provides the structural framework essential for a multitude of cellular processes to occur. We investigated the role of the Arp2/3 complex responsible for branching of actin filaments towards prion formation. Knockout mutants of the nucleation promoting factors of the Arp2/3 complex, in particular the abp1 mutant, showed reduced de novo [PSI+] formation and Sup35 aggregation under basal and oxidative stress conditions. Similarly, treatment with latrunclin A, an actin monomer-sequestering drug also abrogated de novo [PSI+] formation. Colocalization studies revealed that Sup35 often does not colocalize with Rnq1, a marker for the… Advisors/Committee Members: HIGH, STEPHEN S, Grant, Christopher, High, Stephen.

Subjects/Keywords: Prions; Autophagy; Chronological ageing; Actin cytoskeleton; Oxidative stress; Yeast

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Speldewinde, S. H. (2017). Prions, autophagy, ageing and actin cytoskeleton in yeast. (Doctoral Dissertation). University of Manchester. Retrieved from http://www.manchester.ac.uk/escholar/uk-ac-man-scw:308633

Chicago Manual of Style (16^th Edition):

Speldewinde, Shaun Harold. “Prions, autophagy, ageing and actin cytoskeleton in yeast.” 2017. Doctoral Dissertation, University of Manchester. Accessed January 19, 2021. http://www.manchester.ac.uk/escholar/uk-ac-man-scw:308633.

MLA Handbook (7^th Edition):

Speldewinde, Shaun Harold. “Prions, autophagy, ageing and actin cytoskeleton in yeast.” 2017. Web. 19 Jan 2021.

Vancouver:

Speldewinde SH. Prions, autophagy, ageing and actin cytoskeleton in yeast. [Internet] [Doctoral dissertation]. University of Manchester; 2017. [cited 2021 Jan 19]. Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:308633.

Council of Science Editors:

Speldewinde SH. Prions, autophagy, ageing and actin cytoskeleton in yeast. [Doctoral Dissertation]. University of Manchester; 2017. Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:308633

Texas A&M University

26. Henry, James Edward. Development of nano-scale and biomimetic surfaces for biomedical applications.

Degree: PhD, Chemical Engineering, 2006, Texas A&M University

URL: http://hdl.handle.net/1969.1/4395

► The work described in this dissertation details the development of a biomimetic materials for use in sensors and therapeutics, based on new advances in material… (more)

Subjects/Keywords: biomimetic; prions; amyloid; sensor

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Henry, J. E. (2006). Development of nano-scale and biomimetic surfaces for biomedical applications. (Doctoral Dissertation). Texas A&M University. Retrieved from http://hdl.handle.net/1969.1/4395

Chicago Manual of Style (16^th Edition):

Henry, James Edward. “Development of nano-scale and biomimetic surfaces for biomedical applications.” 2006. Doctoral Dissertation, Texas A&M University. Accessed January 19, 2021. http://hdl.handle.net/1969.1/4395.

MLA Handbook (7^th Edition):

Henry, James Edward. “Development of nano-scale and biomimetic surfaces for biomedical applications.” 2006. Web. 19 Jan 2021.

Vancouver:

Henry JE. Development of nano-scale and biomimetic surfaces for biomedical applications. [Internet] [Doctoral dissertation]. Texas A&M University; 2006. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/1969.1/4395.

Council of Science Editors:

Henry JE. Development of nano-scale and biomimetic surfaces for biomedical applications. [Doctoral Dissertation]. Texas A&M University; 2006. Available from: http://hdl.handle.net/1969.1/4395

University of Texas Southwestern Medical Center

27. Cai, Xin. Functional Prions in Mammalian Innate Immune Signaling.

Degree: 2014, University of Texas Southwestern Medical Center

URL: http://hdl.handle.net/2152.5/5285

► Pathogens and cellular danger signals activate mammalian cytosolic sensors such as RIG-I and NLRP3 which signal through respective adaptor proteins MAVS and ASC to produce… (more)

Subjects/Keywords: Biological Evolution; Immunity, Innate; Inflammasomes; Prions; Signal Transduction; Yeasts

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Cai, X. (2014). Functional Prions in Mammalian Innate Immune Signaling. (Thesis). University of Texas Southwestern Medical Center. Retrieved from http://hdl.handle.net/2152.5/5285

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Cai, Xin. “Functional Prions in Mammalian Innate Immune Signaling.” 2014. Thesis, University of Texas Southwestern Medical Center. Accessed January 19, 2021. http://hdl.handle.net/2152.5/5285.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Cai, Xin. “Functional Prions in Mammalian Innate Immune Signaling.” 2014. Web. 19 Jan 2021.

Vancouver:

Cai X. Functional Prions in Mammalian Innate Immune Signaling. [Internet] [Thesis]. University of Texas Southwestern Medical Center; 2014. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/2152.5/5285.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Cai X. Functional Prions in Mammalian Innate Immune Signaling. [Thesis]. University of Texas Southwestern Medical Center; 2014. Available from: http://hdl.handle.net/2152.5/5285

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Washington University in St. Louis

28. Pullen, Melanie Y. Elucidating the Effect of Myopathy-Causing Mutations and Second-Site Suppressors on Client Processing by J-Domain Proteins.

Degree: PhD, Biology & Biomedical Sciences (Developmental, Regenerative, & Stem Cell Biology), 2020, Washington University in St. Louis

URL: https://openscholarship.wustl.edu/art_sci_etds/2233

► Defects in protein quality control may lead to protein misfolding and aggregation often associated with protein conformational disorders such as Alzheimerճ Disease and Limb Girdle… (more)

▼ Defects in protein quality control may lead to protein misfolding and aggregation often associated with protein conformational disorders such as Alzheimerճ Disease and Limb Girdle Muscular Dystrophy, among others. Molecular chaperones protect against protein misfolding and aggregation. A chaperone of interest is the ubiquitously expressed type II Hsp40 co-chaperone DNAJB6, which assists in protein folding and disaggregation. Mutations within the DNAJB6 G/F domain have been associated with the dominantly inherited disease Limb-Girdle Muscular Dystrophy type 1D (LGMD1D), now referred to as LGMDD1. Our collaborators recently discovered novel LGMDD1-associated mutations in the J-domain of DNAJB6. In the enclosed body of work, we used yeast as a model to perform phenotypic, biochemical and functional assays to elucidate the effect of the J-domain mutations on canonical chaperone function with the goal of beginning to understand how mutations in this domain may affect LGMDD1 pathogenesis. Moreover, we have identified second-site suppressors that rescue a viability defect in yeast that is associated with a myopathy-causing mutation. With this work we have begun to assess the ways in which second-site suppressors may be therapeutic for inherited myopathies such as LGMDD1. The heat shock response is a highly conserved program from yeast to mammals, thus, we have used a yeast model system to study disease-causing mutations. The yeast type II Hsp40 co-chaperone, Sis1, is homologous to DNAJB6 and has an important role in yeast for the propagation of two yeast prions, [RNQ+] and [PSI+]. The True lab has previously published work showing that when LGMDD1-associated mutations in the G/F domain are present in Sis1, its client processing function is altered. Since novel J-domain mutations have yet to be characterized, we assessed the effect of these mutations using our yeast model. Here, we provide evidence that novel variants in the Hsp40 J-domain lead to aberrant chaperone function and altered protein homeostasis in a client and conformer specific manner. Moreover, we identified a novel client-dependent viability defect when one of the J-domain mutants is expressed. This is the first time, to our knowledge, that steady-state levels of a mutated chaperone have been shown to be dependent on stabilization by a client. Lastly, we have identified and began to characterize second-site suppressors which may lead future studies into using second-site suppressors for therapeutic purposes. This body of work enables direct comparisons between disease-associated mutants in different domains so that we may begin to not only understand how LGMDD1 mutants could impact disease severity and pathogenesis, but also whether similar therapeutic avenues could be explored to treat patients with different mutations in the future. Advisors/Committee Members: Heather L. True, James Skeath, Yuna Ayala, Conrad Weihl, Hani Zaher.

Subjects/Keywords: chaperones, lgmd1d, lgmdd1, Myopathy, prions, yeast; Biology; Molecular Biology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Pullen, M. Y. (2020). Elucidating the Effect of Myopathy-Causing Mutations and Second-Site Suppressors on Client Processing by J-Domain Proteins. (Doctoral Dissertation). Washington University in St. Louis. Retrieved from https://openscholarship.wustl.edu/art_sci_etds/2233

Chicago Manual of Style (16^th Edition):

Pullen, Melanie Y. “Elucidating the Effect of Myopathy-Causing Mutations and Second-Site Suppressors on Client Processing by J-Domain Proteins.” 2020. Doctoral Dissertation, Washington University in St. Louis. Accessed January 19, 2021. https://openscholarship.wustl.edu/art_sci_etds/2233.

MLA Handbook (7^th Edition):

Pullen, Melanie Y. “Elucidating the Effect of Myopathy-Causing Mutations and Second-Site Suppressors on Client Processing by J-Domain Proteins.” 2020. Web. 19 Jan 2021.

Vancouver:

Pullen MY. Elucidating the Effect of Myopathy-Causing Mutations and Second-Site Suppressors on Client Processing by J-Domain Proteins. [Internet] [Doctoral dissertation]. Washington University in St. Louis; 2020. [cited 2021 Jan 19]. Available from: https://openscholarship.wustl.edu/art_sci_etds/2233.

Council of Science Editors:

Pullen MY. Elucidating the Effect of Myopathy-Causing Mutations and Second-Site Suppressors on Client Processing by J-Domain Proteins. [Doctoral Dissertation]. Washington University in St. Louis; 2020. Available from: https://openscholarship.wustl.edu/art_sci_etds/2233

29. Alleaume-Butaux, Aurélie. Des maladies à prions à la maladie d'Alzheimer : vers l'identification de mécanismes communs de neurodégénérescence : Post transcriptional control of transcripts of AIRE-induced autoantigens in the thymus.

Degree: Docteur es, Biologie cellulaire, 2015, Sorbonne Paris Cité

URL: http://www.theses.fr/2015USPCB100

► Les maladies à prions et d’Alzheimer appartiennent à un groupe de maladies neurodégénératives caractérisées par l’accumulation dans le système nerveux central (SNC) de protéines amyloïdes,… (more)

▼ Les maladies à prions et d’Alzheimer appartiennent à un groupe de maladies neurodégénératives caractérisées par l’accumulation dans le système nerveux central (SNC) de protéines amyloïdes, respectivement la PrPSc et les peptides Aβ. Même si ces maladies ont des étiologies et des manifestations physiopathologiques distinctes, il est suspecté que des mécanismes communs de neurodégénérescence puissent être mobilisés dans ces différentes affections du SNC. Les maladies à prions s’imposent comme un paradigme qui permet l’étude des maladies neurodégénératives amyloïdes. Disposer d’un agent infectieux, la protéine prion scrapie, PrPSc, présente l’avantage de pouvoir initier un processus neurodégénératif et de cerner la nature et la séquence des événements menant à la perte d’homéostasie neuronale. Les mécanismes mis en évidence grâce à l’infection à prions peuvent être objectivés dans d’autres maladies neurodégénératives. Dans les maladies à prions, il est clairement établi que la PrPSc exerce sa toxicité dans les neurones en déviant la/les fonction(s) de la forme non pathologique des prions, la protéine prion cellulaire, PrPC. Les travaux du laboratoire ont permis d’assigner une fonction de signalisation à la PrPC et d’identifier plusieurs intermédiaires de signalisation contrôlés par la PrPC, ce qui a conduit à proposer plusieurs rôles pour la PrPC dans les neurones : régulation de l’équilibre d’oxydoréduction, adhérence, neuritogenèse, survie, contrôle des fonctions associées au neuromédiateur. Une partie de mes travaux de thèse a permis d’illustrer une nouvelle facette de la PrPC dans le contrôle des fonctions neuronales. Au travers d’un couplage à la kinase Lyn et d’une interaction avec la protéine LRP1 et le cuivre, la PrPC du corps cellulaire gouverne l’état d’activation de la kinase GSK3β, qui à son tour, contrôle le trafic et l’activité d’un autorécepteur sérotoninergique, le récepteur 5HT1B. En modulant l’activité de ce récepteur, la PrPC favorise la neurotransmission. A partir de l’infection à prions, mes travaux dévoilent des mécanismes de neurodégénérescence communs aux maladies à prions et à la maladie d’Alzheimer (AD). Dans les neurones infectés par les prions, comme les neurones dérivés de souris modèles pour AD, la suractivation de la kinase PDK1 provoque la phosphorylation et l’internalisation de l’αsécrétase TACE, ce qui annule l’activité neuroprotectrice de TACE à la membrane plasmique. TACE internalisée est découplée de trois de ses substrats, (i) la PrPC, ce qui favorise sa conversion en PrPSc, (ii) la protéine précurseur des peptides amyloïdes APP, ce qui augmente la production des peptides neurotoxiques Aβ et (iii) les récepteurs au TNFα, ce qui rend les neurones malades vulnérables au stress inflammatoire. In vitro comme in vivo, l’inhibition de PDK1 permet de rétablir l’activité neuroprotectrice de TACE et de contrecarrer les effets neurotoxiques de la PrPSc ou de Aβ. Mes travaux établissent également que les Rho kinases (ROCK) sont des régulateurs positifs de l’activité de PDK1. Dans un contexte… Advisors/Committee Members: Schneider, Benoît (thesis director).

Subjects/Keywords: Maladie à prions; Maladie d’Alzheimer; Maladies neurodégénératives; Différenciation neuronale; Signalisation; 571.96

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Alleaume-Butaux, A. (2015). Des maladies à prions à la maladie d'Alzheimer : vers l'identification de mécanismes communs de neurodégénérescence : Post transcriptional control of transcripts of AIRE-induced autoantigens in the thymus. (Doctoral Dissertation). Sorbonne Paris Cité. Retrieved from http://www.theses.fr/2015USPCB100

Chicago Manual of Style (16^th Edition):

Alleaume-Butaux, Aurélie. “Des maladies à prions à la maladie d'Alzheimer : vers l'identification de mécanismes communs de neurodégénérescence : Post transcriptional control of transcripts of AIRE-induced autoantigens in the thymus.” 2015. Doctoral Dissertation, Sorbonne Paris Cité. Accessed January 19, 2021. http://www.theses.fr/2015USPCB100.

MLA Handbook (7^th Edition):

Alleaume-Butaux, Aurélie. “Des maladies à prions à la maladie d'Alzheimer : vers l'identification de mécanismes communs de neurodégénérescence : Post transcriptional control of transcripts of AIRE-induced autoantigens in the thymus.” 2015. Web. 19 Jan 2021.

Vancouver:

Alleaume-Butaux A. Des maladies à prions à la maladie d'Alzheimer : vers l'identification de mécanismes communs de neurodégénérescence : Post transcriptional control of transcripts of AIRE-induced autoantigens in the thymus. [Internet] [Doctoral dissertation]. Sorbonne Paris Cité; 2015. [cited 2021 Jan 19]. Available from: http://www.theses.fr/2015USPCB100.

Council of Science Editors:

Alleaume-Butaux A. Des maladies à prions à la maladie d'Alzheimer : vers l'identification de mécanismes communs de neurodégénérescence : Post transcriptional control of transcripts of AIRE-induced autoantigens in the thymus. [Doctoral Dissertation]. Sorbonne Paris Cité; 2015. Available from: http://www.theses.fr/2015USPCB100

University of Illinois – Chicago

30. Arslan, Fatih. Characterization of De Novo Aggregation of Prions and Protein Misfolding Disease Proteins in Yeast.

Degree: 2015, University of Illinois – Chicago

URL: http://hdl.handle.net/10027/19351

► Many proteins spontaneously misfold, and escape from protein quality mechanisms in the cell. Accumulation of such proteins may become toxic to the host cell. The… (more)

▼ Many proteins spontaneously misfold, and escape from protein quality mechanisms in the cell. Accumulation of such proteins may become toxic to the host cell. The toxic conformers of some proteins often interact with other native forms of the same protein and convert them into the toxic state. These proteins can repeatedly cycle this self-sustaining loop, and exacerbate the cellular proteostatis network, resulting in death. Among such proteins, prions and ALS-linked proteins, FUS and TDP-43, are of great interest to understand the mechanism of de novo appearance of protein misfolding diseases. In this study, I have first studied the de novo appearance of a well-established prion in yeast, [PSI+], and showed that [PSI+] aggregates initially appear at a perivacuolar protein deposit site, where they are converted to amyloid by being cross-seeded via other heterologous protein aggregates. Such an interaction causes continued growth of the de novo [PSI+] fibrils, which requires the molecular chaperones. I also showed that the ALS-linked TDP-43, but not FUS protein can propagate as a self-seeding prion in yeast. Like yeast prions, TDP-43 can form self-seeding aggregates, which are cytoplasmically transmissible, and form detergent resistant oligomers. Unlike yeast prions, the TDP-43 prion causes growth inhibition, and does not require the Hsp104 chaperone for maintenance. In contrast to overexpressed TDP-43 or in vitro TDP-43 fibers, stress does not induce the formation of TDP-43 prions, but can partially cure cells of the TDP-43 prion. The study of the aggregation and toxicity of TDP-43 and FUS in yeast revealed that the yeast prion [PIN+] exacerbates FUS toxicity, and TDP-43 and FUS aggregation. I also showed that the level of the Hsp40 chaperone, Sis1 is vitally important to shear/dissolve and partially detoxify FUS and TDP-43 aggregates in yeast as such aggregates titrate the essential Sis1 protein away from the nucleus. This inhibits Sis1’s function in UPS-mediated delivery of cytosolic misfolded proteins to the nuclear proteasomes, leading to the accumulation of such proteins in the cytosol, and ultimately death. Taken together, insights gained here help us understand the de novo appearance of prions and prion-like disease protein aggregates, and how they cause toxicity in the cell. Advisors/Committee Members: Stone, David E. (advisor), Liebman, Susan W. (committee member), Segev, Nava (committee member), Okkema, Peter (committee member), Li, Liming (committee member).

Subjects/Keywords: prions; TDP-43; FUS; ALS and FTLD; proteostatis; heterologous aggregates

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Arslan, F. (2015). Characterization of De Novo Aggregation of Prions and Protein Misfolding Disease Proteins in Yeast. (Thesis). University of Illinois – Chicago. Retrieved from http://hdl.handle.net/10027/19351

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Arslan, Fatih. “Characterization of De Novo Aggregation of Prions and Protein Misfolding Disease Proteins in Yeast.” 2015. Thesis, University of Illinois – Chicago. Accessed January 19, 2021. http://hdl.handle.net/10027/19351.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Arslan, Fatih. “Characterization of De Novo Aggregation of Prions and Protein Misfolding Disease Proteins in Yeast.” 2015. Web. 19 Jan 2021.

Vancouver:

Arslan F. Characterization of De Novo Aggregation of Prions and Protein Misfolding Disease Proteins in Yeast. [Internet] [Thesis]. University of Illinois – Chicago; 2015. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/10027/19351.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Arslan F. Characterization of De Novo Aggregation of Prions and Protein Misfolding Disease Proteins in Yeast. [Thesis]. University of Illinois – Chicago; 2015. Available from: http://hdl.handle.net/10027/19351

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

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Open Access Theses and Dissertations