subject:(neurodegeneration)

University of Rochester

1. Harder, Jeffrey M. The Role of Bcl-2 Family Members in Retinal Ganglion Cell Death.

Degree: PhD, 2013, University of Rochester

► Glaucomas are a group of diseases that often lead to blindness. Glaucomas are unified by the characteristic cell death of the output neuron of the… (more)

▼ Glaucomas are a group of diseases that often lead to blindness. Glaucomas are unified by the characteristic cell death of the output neuron of the retina, the retinal ganglion cell (RGC). In glaucoma, axonal injury to RGCs is a key event that precipitates their death; however, the molecular mechanisms leading to RGC death after axonal injury remain unclear. In fact, only one molecule, BAX, has been shown to be necessary for glaucomatous RGC death. BAX is a member of the Bcl-2 family of apoptotic regulators and BAX activation is a final step in triggering apoptosis. Other Bcl-2 family members can interact with BAX and regulate its activity. Identifying the Bcl-2 family members that mediate BAX activation in RGCs is an important step toward defining the cell signaling pathways responsible for RGC death in glaucoma. This work investigates the contributions of Bcl-2 family members implicated in RGC death in vivo using mice with specific Bcl-2 family genes deleted. Based on their function, the pro-death Bcl-2 family members BIM, BBC3, and BID are the primary candidates to mediate BAX activation in RGCs. BAX activation is highly potentiated by, if not requires, direct binding between BAX and these pro-death molecules. In mice lacking these genes, RGC death following axonal injury was significantly delayed. These experiments uncovered the additive, but hierarchical nature of BIM, BBC3, and BID function in RGCs. However, these molecules were not required for RGC death after axonal injury. Although BIM potently induced RGC death after axonal injury, the loss of RGCs in a mouse model of pigmentary glaucoma was also not prevented in a Bim knockout mouse. In RGCs, alternative BAX activation may occur following inhibition of pro-survival Bcl-2 family members. BCL-X was identified as an active endogenous factor that promotes RGC survival in the adult after axonal injury. However, disrupting other pro-death Bcl-2 family members, who primarily function to antagonize BCL-X, did not alter RGC death. The results provide insight into the specific and multifaceted nature of BAX activation in RGCs and point to an important interaction between pro-survival and pro-death signaling leading to RGC death in glaucoma.

Subjects/Keywords: Neurodegeneration

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

APA (6^th Edition):

Harder, J. M. (2013). The Role of Bcl-2 Family Members in Retinal Ganglion Cell Death. (Doctoral Dissertation). University of Rochester. Retrieved from http://hdl.handle.net/1802/26812

Chicago Manual of Style (16^th Edition):

Harder, Jeffrey M. “The Role of Bcl-2 Family Members in Retinal Ganglion Cell Death.” 2013. Doctoral Dissertation, University of Rochester. Accessed July 22, 2019. http://hdl.handle.net/1802/26812.

MLA Handbook (7^th Edition):

Harder, Jeffrey M. “The Role of Bcl-2 Family Members in Retinal Ganglion Cell Death.” 2013. Web. 22 Jul 2019.

Vancouver:

Harder JM. The Role of Bcl-2 Family Members in Retinal Ganglion Cell Death. [Internet] [Doctoral dissertation]. University of Rochester; 2013. [cited 2019 Jul 22]. Available from: http://hdl.handle.net/1802/26812.

Council of Science Editors:

Harder JM. The Role of Bcl-2 Family Members in Retinal Ganglion Cell Death. [Doctoral Dissertation]. University of Rochester; 2013. Available from: http://hdl.handle.net/1802/26812

Cornell University

2. Brady, Owen. Investigating Mechanisms Of Ftld-Tdp Pathogenesis .

Degree: 2014, Cornell University

URL: http://hdl.handle.net/1813/36146

► Frontotemporal lobar degeneration (FTLD) is a devastating dementia disorder that causes profound changes in personality, behavior, and language abilities. Major breakthroughs in the past decade… (more)

▼ Frontotemporal lobar degeneration (FTLD) is a devastating dementia disorder that causes profound changes in personality, behavior, and language abilities. Major breakthroughs in the past decade have advanced the understanding of the molecular genetics and pathological mechanisms underlying this disease, in particular the most common subtype, FTLD-TDP. Several causative and risk modifying genes have been identified which implicate defects in protein degradation and RNA metabolism pathways. The work presented here can be split into two main projects. In the first, I examine the physical properties of TDP-43 aggregation, which is a hallmark of FTLDTDP. Specifically, I characterize the role that phosphorylation plays in mediating the aggregation propensity of TDP-43 in a mammalian cell culture system. I further show that TDP-43 aggregates are cleared by the autophagy lysosome and ubiquitin proteasome systems, with the ubiquitin binding adaptor protein, p62/SQSTM1 facilitating this process. In the second project, I sought to characterize the recently identified FTLD-TDP risk factor, TMEM106B. Using cell culture model systems, I demonstrate that TMEM106B overexpression causes specific defects in lysosome size, morphology, and degradative capacity. I also ruled out the effect of a small coding variant associated with the TMEM106B risk allele when the proteins are highly expressed at the same level, indicating that increased TMEM106B levels are the likely cause of defects seen in certain cases of FTLD-TDP. I have also identified a putative degradation pathway implicating lumenal lysosomal enzymes and a membrane bound intramembrane protease, SPPL2a, in the sequential proteolysis of TMEM106B. This pathway may represent a novel therapeutic target for controlling TMEM106B levels in vivo. Overall, my work has contributed significant findings to the field of FTLD-TDP related research and has increased the body of knowledge regarding the cellular and molecular mechanisms that contribute to this terrible disease. Advisors/Committee Members: Lin, David M. (committeeMember), Brown, William J (committeeMember).

Subjects/Keywords: Neurodegeneration; Lysosomes; TMEM106B

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APA (6^th Edition):

Brady, O. (2014). Investigating Mechanisms Of Ftld-Tdp Pathogenesis . (Thesis). Cornell University. Retrieved from http://hdl.handle.net/1813/36146

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):

Brady, Owen. “Investigating Mechanisms Of Ftld-Tdp Pathogenesis .” 2014. Thesis, Cornell University. Accessed July 22, 2019. http://hdl.handle.net/1813/36146.

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

MLA Handbook (7^th Edition):

Brady, Owen. “Investigating Mechanisms Of Ftld-Tdp Pathogenesis .” 2014. Web. 22 Jul 2019.

Vancouver:

Brady O. Investigating Mechanisms Of Ftld-Tdp Pathogenesis . [Internet] [Thesis]. Cornell University; 2014. [cited 2019 Jul 22]. Available from: http://hdl.handle.net/1813/36146.

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

Council of Science Editors:

Brady O. Investigating Mechanisms Of Ftld-Tdp Pathogenesis . [Thesis]. Cornell University; 2014. Available from: http://hdl.handle.net/1813/36146

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

University of Miami

3. Tseng, LeinWeih Andrew. Ubiquitylation of Neuronal Pentraxin with Chromo Domain by the E3 Ubiquitin Ligase Mayven/KLHL2 and Effects on Aggresome Formation and Neuronal Cytotoxicity.

Degree: PhD, Molecular and Cellular Pharmacology (Medicine), 2010, University of Miami

URL: https://scholarlyrepository.miami.edu/oa_dissertations/662

► Neuronal pentraxin with chromo domain (NPCD) belongs to a family of neuronally-expressed pentraxin proteins thought to be involved in synaptic refinement and plasticity. One isoform… (more)

▼ Neuronal pentraxin with chromo domain (NPCD) belongs to a family of neuronally-expressed pentraxin proteins thought to be involved in synaptic refinement and plasticity. One isoform of Npcd, neuronal pentraxin receptor (NPR), is a type-II transmembrane protein responsible for the clustering of related neuronal pentraxins 1 and 2. However, recently identified cytosolic NPCD isoforms with no known function were discovered through their interaction with the intracellular domain of a receptor protein tyrosine phosphatase PTPRO. PTPRO is a signaling molecule known to be involved in the development of the nervous system. Additionally, upregulated expression of neuronal pentraxins has been implicated in neuronal cytotoxicity and associated with neurodegenerative diseases. Here, we demonstrate that a novel cytosolic NPCD isoform interacts with the BTB-Kelch protein Mayven/KLHL2. This interaction was identified through a yeast two-hybrid screen using the C-terminal pentraxin domain region of NPCD and confirmed through mammalian cell colocalization and co-immunoprecipitation studies. Domain truncation analysis suggests that the kelch domains of Mayven/KLHL2 are responsible for this interaction with NPCD. We also show that Mayven/KLHL2 is capable of interacting with Cullin 3, an integral protein in the Cullin-RING ubiquitin ligase complex. An in-vivo ubiquitylation assay demonstrates that overexpression of Mayven/KLHL2 increases NPCD ubiquitylation, and suggests a novel E3 ubiquitin ligase function of Mayven/KLHL2 with NPCD as its substrate. Furthermore, we observed an increased propensity of overexpressed NPCD to form aggresomes with coexpression of Mayven/KLHL2. As the formation of aggresomes is often associated with protein aggregation and deposition diseases, including a multitude of neurodegenerative diseases, we tested NPCD overexpression and the effects of Mayven/KLHL2 coexpression on neuronal cytotoxicity and apoptosis. Overexpressed NPCD in hippocampal neuron cultures resulted in increased cytotoxicity and apoptosis, further exacerbated by Mayven/KLHL2 coexpression. Our findings report an interaction between NPCD and Mayven/KLHL2, demonstrate a novel role of Mayven/KLHL2 as an E3 ubiquitin ligase, and explore a possible intersection between the ubiquitin-proteasome degradation pathway, neuronal pentraxins, and neurodegenerative disease. Advisors/Committee Members: Fulvia Verde - Committee Chair, Sandra Lemmon - Committee Member, Abigail Hackam - Committee Member, John Bixby - Mentor, Nagi Ayad - Outside Committee Member.

Subjects/Keywords: Protein Aggregation; Neurodegeneration

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

APA (6^th Edition):

Tseng, L. A. (2010). Ubiquitylation of Neuronal Pentraxin with Chromo Domain by the E3 Ubiquitin Ligase Mayven/KLHL2 and Effects on Aggresome Formation and Neuronal Cytotoxicity. (Doctoral Dissertation). University of Miami. Retrieved from https://scholarlyrepository.miami.edu/oa_dissertations/662

Chicago Manual of Style (16^th Edition):

Tseng, LeinWeih Andrew. “Ubiquitylation of Neuronal Pentraxin with Chromo Domain by the E3 Ubiquitin Ligase Mayven/KLHL2 and Effects on Aggresome Formation and Neuronal Cytotoxicity.” 2010. Doctoral Dissertation, University of Miami. Accessed July 22, 2019. https://scholarlyrepository.miami.edu/oa_dissertations/662.

MLA Handbook (7^th Edition):

Tseng, LeinWeih Andrew. “Ubiquitylation of Neuronal Pentraxin with Chromo Domain by the E3 Ubiquitin Ligase Mayven/KLHL2 and Effects on Aggresome Formation and Neuronal Cytotoxicity.” 2010. Web. 22 Jul 2019.

Vancouver:

Tseng LA. Ubiquitylation of Neuronal Pentraxin with Chromo Domain by the E3 Ubiquitin Ligase Mayven/KLHL2 and Effects on Aggresome Formation and Neuronal Cytotoxicity. [Internet] [Doctoral dissertation]. University of Miami; 2010. [cited 2019 Jul 22]. Available from: https://scholarlyrepository.miami.edu/oa_dissertations/662.

Council of Science Editors:

Tseng LA. Ubiquitylation of Neuronal Pentraxin with Chromo Domain by the E3 Ubiquitin Ligase Mayven/KLHL2 and Effects on Aggresome Formation and Neuronal Cytotoxicity. [Doctoral Dissertation]. University of Miami; 2010. Available from: https://scholarlyrepository.miami.edu/oa_dissertations/662

University of Miami

4. Tseng, LeinWeih Andrew. Ubiquitylation of Neuronal Pentraxin with Chromo Domain by the E3 Ubiquitin Ligase Mayven/KLHL2 and Effects on Aggresome Formation and Neuronal Cytotoxicity.

Degree: PhD, Molecular and Cellular Pharmacology (Medicine), 2010, University of Miami

URL: https://scholarlyrepository.miami.edu/oa_dissertations/928

► Neuronal pentraxin with chromo domain (NPCD) belongs to a family of neuronally-expressed pentraxin proteins thought to be involved in synaptic refinement and plasticity. One isoform… (more)

▼ Neuronal pentraxin with chromo domain (NPCD) belongs to a family of neuronally-expressed pentraxin proteins thought to be involved in synaptic refinement and plasticity. One isoform of Npcd, neuronal pentraxin receptor (NPR), is a type-II transmembrane protein responsible for the clustering of related neuronal pentraxins 1 and 2. However, recently identified cytosolic NPCD isoforms with no known function were discovered through their interaction with the intracellular domain of a receptor protein tyrosine phosphatase PTPRO. PTPRO is a signaling molecule known to be involved in the development of the nervous system. Additionally, upregulated expression of neuronal pentraxins has been implicated in neuronal cytotoxicity and associated with neurodegenerative diseases. Here, we demonstrate that a novel cytosolic NPCD isoform interacts with the BTB-Kelch protein Mayven/KLHL2. This interaction was identified through a yeast two-hybrid screen using the C-terminal pentraxin domain region of NPCD and confirmed through mammalian cell colocalization and co-immunoprecipitation studies. Domain truncation analysis suggests that the kelch domains of Mayven/KLHL2 are responsible for this interaction with NPCD. We also show that Mayven/KLHL2 is capable of interacting with Cullin 3, an integral protein in the Cullin-RING ubiquitin ligase complex. An in-vivo ubiquitylation assay demonstrates that overexpression of Mayven/KLHL2 increases NPCD ubiquitylation, and suggests a novel E3 ubiquitin ligase function of Mayven/KLHL2 with NPCD as its substrate. Furthermore, we observed an increased propensity of overexpressed NPCD to form aggresomes with coexpression of Mayven/KLHL2. As the formation of aggresomes is often associated with protein aggregation and deposition diseases, including a multitude of neurodegenerative diseases, we tested NPCD overexpression and the effects of Mayven/KLHL2 coexpression on neuronal cytotoxicity and apoptosis. Overexpressed NPCD in hippocampal neuron cultures resulted in increased cytotoxicity and apoptosis, further exacerbated by Mayven/KLHL2 coexpression. Our findings report an interaction between NPCD and Mayven/KLHL2, demonstrate a novel role of Mayven/KLHL2 as an E3 ubiquitin ligase, and explore a possible intersection between the ubiquitin-proteasome degradation pathway, neuronal pentraxins, and neurodegenerative disease. Advisors/Committee Members: Fulvia Verde - Committee Chair, Sandra Lemmon - Committee Member, Abigail Hackam - Committee Member, John Bixby - Mentor, Nagi Ayad - Outside Committee Member.

Subjects/Keywords: Protein Aggregation; Neurodegeneration

Record Details Similar Records Cite « Share

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

APA (6^th Edition):

Tseng, L. A. (2010). Ubiquitylation of Neuronal Pentraxin with Chromo Domain by the E3 Ubiquitin Ligase Mayven/KLHL2 and Effects on Aggresome Formation and Neuronal Cytotoxicity. (Doctoral Dissertation). University of Miami. Retrieved from https://scholarlyrepository.miami.edu/oa_dissertations/928

Chicago Manual of Style (16^th Edition):

Tseng, LeinWeih Andrew. “Ubiquitylation of Neuronal Pentraxin with Chromo Domain by the E3 Ubiquitin Ligase Mayven/KLHL2 and Effects on Aggresome Formation and Neuronal Cytotoxicity.” 2010. Doctoral Dissertation, University of Miami. Accessed July 22, 2019. https://scholarlyrepository.miami.edu/oa_dissertations/928.

MLA Handbook (7^th Edition):

Tseng, LeinWeih Andrew. “Ubiquitylation of Neuronal Pentraxin with Chromo Domain by the E3 Ubiquitin Ligase Mayven/KLHL2 and Effects on Aggresome Formation and Neuronal Cytotoxicity.” 2010. Web. 22 Jul 2019.

Vancouver:

Tseng LA. Ubiquitylation of Neuronal Pentraxin with Chromo Domain by the E3 Ubiquitin Ligase Mayven/KLHL2 and Effects on Aggresome Formation and Neuronal Cytotoxicity. [Internet] [Doctoral dissertation]. University of Miami; 2010. [cited 2019 Jul 22]. Available from: https://scholarlyrepository.miami.edu/oa_dissertations/928.

Council of Science Editors:

Tseng LA. Ubiquitylation of Neuronal Pentraxin with Chromo Domain by the E3 Ubiquitin Ligase Mayven/KLHL2 and Effects on Aggresome Formation and Neuronal Cytotoxicity. [Doctoral Dissertation]. University of Miami; 2010. Available from: https://scholarlyrepository.miami.edu/oa_dissertations/928

University of Arizona

5. Coyne, Alyssa N. Dysregulation of mRNA Transport and Translation in ALS .

Degree: 2016, University of Arizona

URL: http://hdl.handle.net/10150/623181

► Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease affecting upper and lower motor neurons. Although many cellular processes such as cytoskeletal maintenance and synaptic… (more)

▼ Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease affecting upper and lower motor neurons. Although many cellular processes such as cytoskeletal maintenance and synaptic function are disrupted in ALS, the molecular mechanisms by which these defects arise remain poorly understood. TDP-43, an RNA binding protein linked to the majority of ALS cases, is involved in multiple aspects of RNA metabolism. It is hypothesized that TDP-43 may sequester its mRNA targets into cytoplasmic stress granules during disease progression in turn, inhibiting their localization and/or translation. This work uses a Drosophila model of ALS based on TDP-43, to provide evidence for TDP-43’s role in translation regulation of specific mRNA targets. Using a combination of genetic, molecular, and imaging approaches this work has identified TDP-43 induced post-transcriptional alterations in futsch and hsc70-4 mRNAs. First, futsch/MAP1B is a TDP-43 mRNA target altered at the level of mRNA localization and translation. This results in microtubule instability at the NMJ as evidenced by an increased number of satellite boutons and decreased number of Futsch positive loops that are thought to indicate stable synaptic contacts. Furthermore, overexpression of Futsch mitigates defects in microtubule stability and TDP-43 dependent locomotor dysfunction and also increases lifespan. Second, this work shows that synaptic expression of Hsc70-4, a molecular chaperone critical for synaptic vesicle cycling is involved in multiple steps of the synaptic vesicle cycle, is reduced at the NMJ when TDP-43 is overexpressed in motor neurons. Using a combination of electrophysiology and FM1-43 dye uptake assays, this work shows that motor neuron expression of TDP-43 induces defects in synaptic vesicle endocytosis. Third, this work identifies Fragile X Protein (FMRP) as a neuroprotective protein partner of TDP-43. FMRP overexpression remodels RNP granules, extracts TDP-43 from insoluble complexes, and restores the translation of specific TDP-43 targets. Together, these data provides evidence for translation dysregulation underlying microtubule instability and synaptic dysfunction in ALS pathogenesis and identifies restoration of translation via remodeling RNP granules as a neuroprotective strategy to mitigate toxicity. Advisors/Committee Members: Zarnescu, Daniela C (advisor), Zarnescu, Daniela C. (committeemember), Zinsmaier, Konrad (committeemember), Buchan, John (committeemember), Madhavan, Lalitha (committeemember).

Subjects/Keywords: Drosophila; neurodegeneration; ALS

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

APA (6^th Edition):

Coyne, A. N. (2016). Dysregulation of mRNA Transport and Translation in ALS . (Doctoral Dissertation). University of Arizona. Retrieved from http://hdl.handle.net/10150/623181

Chicago Manual of Style (16^th Edition):

Coyne, Alyssa N. “Dysregulation of mRNA Transport and Translation in ALS .” 2016. Doctoral Dissertation, University of Arizona. Accessed July 22, 2019. http://hdl.handle.net/10150/623181.

MLA Handbook (7^th Edition):

Coyne, Alyssa N. “Dysregulation of mRNA Transport and Translation in ALS .” 2016. Web. 22 Jul 2019.

Vancouver:

Coyne AN. Dysregulation of mRNA Transport and Translation in ALS . [Internet] [Doctoral dissertation]. University of Arizona; 2016. [cited 2019 Jul 22]. Available from: http://hdl.handle.net/10150/623181.

Council of Science Editors:

Coyne AN. Dysregulation of mRNA Transport and Translation in ALS . [Doctoral Dissertation]. University of Arizona; 2016. Available from: http://hdl.handle.net/10150/623181

University of Edinburgh

6. Vincenti, James Edward. Role of activation of microglia in neurodegenerative prion disease.

Degree: PhD, 2015, University of Edinburgh

URL: http://hdl.handle.net/1842/15928

► Prion diseases are a group of fatal neurodegenerative protein-misfolding diseases. Microglia, the resident myeloid cells found within the brain, have been shown to demonstrate a… (more)

▼ Prion diseases are a group of fatal neurodegenerative protein-misfolding diseases. Microglia, the resident myeloid cells found within the brain, have been shown to demonstrate a reactive morphology during the disease process with conflicting evidence for both a neurotoxic and neuroprotective role. The studies presented here aimed to investigate the role of microglia activation using transcriptomic and morphological analysis of prion disease in mice. Initially, the host immune response to prion disease was explored using a publically available mouse prion disease dataset. Re-analysis of this dataset was performed using BioLayout Express3D; a novel software tool that supports the visualisation and clustering of correlation networks. Disease-associated genes up-regulated during the later stages of infection were present in two main clusters. The cellular origin of these genes was explored by examining their expression in a dataset comprised of pure populations of cells. This demonstrated that the primary cluster of up-regulated transcripts encompassed genes expressed mainly by microglia and to a lesser extent astrocytes and neurons. The secondary cluster comprised almost exclusively of interferon response genes. The conclusions of these analyses were different from those of the original study that suggested disease-associated genes were primarily neuronal in origin. Mouse models of prion disease were established by infecting a novel line of BALB/cJ inbred mice, expressing EGFP under control of a myeloid specific Csf1r promoter, with the 79A prion strain. Quantification of the morphological changes of EGFP expressing microglia suggested the cells accumulated in the medulla at sites of early misfolded protein deposition with minimal change in their overall appearance. An activated microglia morphology was not observed until protein deposition was extensive. Isolation of EGFP expressing microglia was performed for transcriptome analysis. The vast majority of disease associated genes demonstrated increased expression at the onset of clinical symptoms. The gene list was found to be highly enriched for genes associated with an innate immune response regulated by the NFκB signalling cascade. Also highly enriched were processes associated with protein translation, energy production and stress response. These data suggest a high metabolic load is burdened by proliferating microglia; and as part of a response which is strikingly more pro-inflammatory in nature than has previously been attributed to the microglia phenotype within prion disease. As an active contributor to normal homeostasis, microglia are more than just innate immune surveillance and are now considered an integral component in both the healthy and diseased brain. The ramifications of activation toward the microglia phenotype shown here will have direct and potentially cytotoxic influence on neighbouring microglia and other brain cell types implying microglia as major contributors to the neurotoxic environment found within the CNS during prion disease. Furthermore…

Subjects/Keywords: 612.8; microglia; neurodegeneration; neuroimmunology; prion

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

APA (6^th Edition):

Vincenti, J. E. (2015). Role of activation of microglia in neurodegenerative prion disease. (Doctoral Dissertation). University of Edinburgh. Retrieved from http://hdl.handle.net/1842/15928

Chicago Manual of Style (16^th Edition):

Vincenti, James Edward. “Role of activation of microglia in neurodegenerative prion disease.” 2015. Doctoral Dissertation, University of Edinburgh. Accessed July 22, 2019. http://hdl.handle.net/1842/15928.

MLA Handbook (7^th Edition):

Vincenti, James Edward. “Role of activation of microglia in neurodegenerative prion disease.” 2015. Web. 22 Jul 2019.

Vancouver:

Vincenti JE. Role of activation of microglia in neurodegenerative prion disease. [Internet] [Doctoral dissertation]. University of Edinburgh; 2015. [cited 2019 Jul 22]. Available from: http://hdl.handle.net/1842/15928.

Council of Science Editors:

Vincenti JE. Role of activation of microglia in neurodegenerative prion disease. [Doctoral Dissertation]. University of Edinburgh; 2015. Available from: http://hdl.handle.net/1842/15928

Kent State University

7. Kumar, Varun. Protein Kinase C Signaling in Neurodegeneration.

Degree: PhD, College of Arts and Sciences / School of Biomedical Sciences, 2016, Kent State University

URL: http://rave.ohiolink.edu/etdc/view?acc_num=kent1455721051

► Global cerebral ischemia occurs due to cardiac arrest, which results in delayed neurodegeneration. Pharmacological agents such as Protein Kinase C epsilon (PKC epsilon) peptide activators… (more)

▼ Global cerebral ischemia occurs due to cardiac arrest, which results in delayed neurodegeneration. Pharmacological agents such as Protein Kinase C epsilon (PKC epsilon) peptide activators when applied before ischemia are known to confer neuroprotection against ischemia-induced cell death. However, the occurrence of cardiac arrest or cerebral ischemia is unpredictable. Thus, therapeutic targets that can be applied after ischemia have to be unraveled. Moreover, the effect of PKC epsilon deletion after global cerebral ischemia has not been studied yet. Therefore, we have studied the effect of PKC epsilon deletion after global cerebral ischemia. Using mouse model of global cerebral ischemia, we found that hippocampal neurodegeneration was significantly reduced in knock-out (KO) mice compared with PKC epsilon wild-type (WT) mice three days after ischemia. To determine the mechanisms underlying the role of PKC epsilon in ischemia-induced neurodegeneration, we have investigated the role of activating transcription factor 2 (ATF2) and found that PKC epsilon regulates the subcellular localization of ATF2 via Threonine 52 (Thr52) phosphorylation and mediates apoptosis in hippocampal neurons. This study will give insight into the role of PKC epsilon-ATF2 signaling and other PKC isozymes in hippocampal neurons after global cerebral ischemia. PKC delta, another member of novel PKC family, has been implicated in stroke-reperfusion injury. To better study the role of PKC delta in normal function and disease, we have developed an ATP analog-specific PKC delta (AS-PKC delta) that is sensitive to specific kinase inhibitors and can be used to identify PKC delta substrates. To understand the mechanisms for specificity and affinity of these analogs, we have created in silico WT and AS-PKC delta homology models based on the crystal structure of Protein Kinase C iota (PKC iota). N6-(benzyl)-ATP and ATP showed similar positioning within the purine binding pocket of AS-PKC delta, while N6-(benzyl)-ATP was displaced from the pocket of WT-PKC delta and was unable to interact with the glycine-rich loop that is required for phosphoryl-transfer. The adenine ring of 1NA-PP1 and 2MB-PP1 matched the adenine ring of ATP when docked in AS-PKC delta and this interaction prevented the potential binding of ATP with Lys-378, Glu-428, and Leu-430 residues. 1NA-PP1 failed to effectively dock within WT-PKC delta. Moreover, other PP1 analogs failed effectively to interact with either AS-PKC delta or WT-PKC delta. These results provide a structural basis for the ability of AS-PKC delta to efficiently and specifically utilize N6-(benzyl)-ATP as a phosphate donor, and for its selective inhibition by 1NA-PP1 and 2MB-PP1. Such homology modeling could prove useful in designing molecules to target PKC delta and other kinases to understand their function in cell signaling and to identify unique substrates. Advisors/Committee Members: Chou, Wen-Hai (Advisor).

Subjects/Keywords: Neurobiology; PKC, Neurodegeneration, ATF2

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APA (6^th Edition):

Kumar, V. (2016). Protein Kinase C Signaling in Neurodegeneration. (Doctoral Dissertation). Kent State University. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=kent1455721051

Chicago Manual of Style (16^th Edition):

Kumar, Varun. “Protein Kinase C Signaling in Neurodegeneration.” 2016. Doctoral Dissertation, Kent State University. Accessed July 22, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=kent1455721051.

MLA Handbook (7^th Edition):

Kumar, Varun. “Protein Kinase C Signaling in Neurodegeneration.” 2016. Web. 22 Jul 2019.

Vancouver:

Kumar V. Protein Kinase C Signaling in Neurodegeneration. [Internet] [Doctoral dissertation]. Kent State University; 2016. [cited 2019 Jul 22]. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=kent1455721051.

Council of Science Editors:

Kumar V. Protein Kinase C Signaling in Neurodegeneration. [Doctoral Dissertation]. Kent State University; 2016. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=kent1455721051

University of Sydney

8. Cross, Nathan. Obstructive sleep apnoea in older adults: Predictors of cognitive decline and neurodegeneration .

Degree: 2017, University of Sydney

URL: http://hdl.handle.net/2123/17763

► There is growing evidence that sleep disturbances share associations with neurodegeneration, and poor sleep is emerging as an independent risk factor for dementia. As a… (more)

▼ There is growing evidence that sleep disturbances share associations with neurodegeneration, and poor sleep is emerging as an independent risk factor for dementia. As a common sleep disorder, obstructive sleep apnea (OSA) has been connected to compromised cognition, brain integrity and an increased risk for dementia. However, there is a need to clarify these relationships in older adults and understand the mechanisms underpinning the link between OSA and cognitive decline. The aims of this thesis were: 1) to characterise and quantitatively analyse the relationship between OSA and cognitive function in older adults, 2) to determine whether any changes in neural oscillations during sleep or brain grey matter thickness and volume, might be associated with OSA and related to makers of cognitive decline (e.g. memory) in a sample of older adults at-risk for dementia. At-risk adults were diagnosed as health-seeking older adults (>50 years) with subjective or objective cognitive impairment. Neural oscillations were recorded using electroencephalography and brain grey matter thickness and volume were measured using magnetic resonance imaging. These findings showed that the presence of OSA in at-risk older adults is related to a marked reduction in specific neural oscillations (sleep spindles), key aspects of sleep microarchitecture that are integrally linked with memory consolidation. Furthermore, OSA-related oxygen desaturation was associated with decreased cortical thickness in both the left and right temporal lobes, while sleep disturbance was related to increased cortical thickness in in frontal, central and occipital regions of the right cortex. This work has provided evidence that OSA is related to features which may contribute to early-stage neurodegeneration and cognitive decline, which are important in identifying critical periods for intervention. Given that effective treatment exists for OSA, efforts to increase OSA screening in older adults are now warranted.

Subjects/Keywords: sleep; apnoea; ageing; neurodegeneration

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

APA (6^th Edition):

Cross, N. (2017). Obstructive sleep apnoea in older adults: Predictors of cognitive decline and neurodegeneration . (Thesis). University of Sydney. Retrieved from http://hdl.handle.net/2123/17763

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):

Cross, Nathan. “Obstructive sleep apnoea in older adults: Predictors of cognitive decline and neurodegeneration .” 2017. Thesis, University of Sydney. Accessed July 22, 2019. http://hdl.handle.net/2123/17763.

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

MLA Handbook (7^th Edition):

Cross, Nathan. “Obstructive sleep apnoea in older adults: Predictors of cognitive decline and neurodegeneration .” 2017. Web. 22 Jul 2019.

Vancouver:

Cross N. Obstructive sleep apnoea in older adults: Predictors of cognitive decline and neurodegeneration . [Internet] [Thesis]. University of Sydney; 2017. [cited 2019 Jul 22]. Available from: http://hdl.handle.net/2123/17763.

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

Council of Science Editors:

Cross N. Obstructive sleep apnoea in older adults: Predictors of cognitive decline and neurodegeneration . [Thesis]. University of Sydney; 2017. Available from: http://hdl.handle.net/2123/17763

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

University of Debrecen

9. Seo, Woo Sung. Role of p53 and PARP-1 in neurodegenerative diseases .

Degree: DE – Általános Orvostudományi Kar, University of Debrecen

URL: http://hdl.handle.net/2437/243137

► The thesis presents a general review of major neurodegenerative diseases and also discusses the role of p53 and PARP-1 in neurodegeneration. p53 and PARP-1 are… (more)

Subjects/Keywords: Neurodegeneration; neuroscience

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

APA (6^th Edition):

Seo, W. S. (n.d.). Role of p53 and PARP-1 in neurodegenerative diseases . (Thesis). University of Debrecen. Retrieved from http://hdl.handle.net/2437/243137

Note: this citation may be lacking information needed for this citation format:
No year of publication.
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Seo, Woo Sung. “Role of p53 and PARP-1 in neurodegenerative diseases .” Thesis, University of Debrecen. Accessed July 22, 2019. http://hdl.handle.net/2437/243137.

Note: this citation may be lacking information needed for this citation format:
No year of publication.
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Seo, Woo Sung. “Role of p53 and PARP-1 in neurodegenerative diseases .” Web. 22 Jul 2019.

Note: this citation may be lacking information needed for this citation format:
No year of publication.

Vancouver:

Seo WS. Role of p53 and PARP-1 in neurodegenerative diseases . [Internet] [Thesis]. University of Debrecen; [cited 2019 Jul 22]. Available from: http://hdl.handle.net/2437/243137.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
No year of publication.

Council of Science Editors:

Seo WS. Role of p53 and PARP-1 in neurodegenerative diseases . [Thesis]. University of Debrecen; Available from: http://hdl.handle.net/2437/243137

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
No year of publication.

University of Manchester

10. Howard, Daniel. The role of the cytoskeleton in Alzheimer’s disease: a Drosophila perspective.

Degree: 2016, University of Manchester

URL: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:300556

► Alzheimer’s disease (AD) pathogenesis is likely to be caused by dysfunction of two neuronal proteins, amyloid-beta (Aβ) and tau. Whilst excellent in vivo assays have… (more)

Subjects/Keywords: drosophila; neurodegeneration; amyloid; tau

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APA (6^th Edition):

Howard, D. (2016). The role of the cytoskeleton in Alzheimer’s disease: a Drosophila perspective. (Doctoral Dissertation). University of Manchester. Retrieved from http://www.manchester.ac.uk/escholar/uk-ac-man-scw:300556

Chicago Manual of Style (16^th Edition):

Howard, Daniel. “The role of the cytoskeleton in Alzheimer’s disease: a Drosophila perspective.” 2016. Doctoral Dissertation, University of Manchester. Accessed July 22, 2019. http://www.manchester.ac.uk/escholar/uk-ac-man-scw:300556.

MLA Handbook (7^th Edition):

Howard, Daniel. “The role of the cytoskeleton in Alzheimer’s disease: a Drosophila perspective.” 2016. Web. 22 Jul 2019.

Vancouver:

Howard D. The role of the cytoskeleton in Alzheimer’s disease: a Drosophila perspective. [Internet] [Doctoral dissertation]. University of Manchester; 2016. [cited 2019 Jul 22]. Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:300556.

Council of Science Editors:

Howard D. The role of the cytoskeleton in Alzheimer’s disease: a Drosophila perspective. [Doctoral Dissertation]. University of Manchester; 2016. Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:300556

University of Cambridge

11. Sohail, Anood. Visualizing Roles of Spastic Paraplegia Proteins in Organizing Axonal ER in Live Drosophila .

Degree: 2019, University of Cambridge

URL: https://www.repository.cam.ac.uk/handle/1810/290113

► Axons possess a continuous network of smooth tubular endoplasmic reticulum (ER), extending from the nuclear envelope throughout the neuron to synapses. Mutations affecting proteins with… (more)

▼ Axons possess a continuous network of smooth tubular endoplasmic reticulum (ER), extending from the nuclear envelope throughout the neuron to synapses. Mutations affecting proteins with intramembrane hairpin domains that model tubular ER membrane can lead to the axon degenerative disease, hereditary spastic paraplegia (HSP). However, the extent and mechanisms by which HSP proteins contribute to axonal ER organization and dynamics are unclear. To understand these mechanisms, there is a need to visualize axonal ER in wild-type and mutant live axons. I have therefore aimed to develop these tools in Drosophila larvae and adults, and use them to visualize mutant phenotypes. Firstly, I developed a system to visualize fluorescently marked ER in individual axons in adult fly legs, and tested how this can be used to investigate the effects of loss of intramembrane hairpin HSP proteins on ER in adult legs. Secondly, known mutations affecting HSP hairpin proteins reduce the axonal ER network but not severely; I hypothesized that additional HSP ER membrane proteins might contribute to residual tubule formation; these include Arl6IP, also reported to promote ER tubule formation. I generated transgenic flies to overexpress a fluorescently tagged eGFP::Arl6IP1, and found that this fusion protein localizes within axonal ER. To study whether loss of Arl6IP1 function affects axonal ER, I tested the effects of knockdown on this compartment, but found no consistent effects. To achieve stronger loss of function, I also generated a mutant stock that lacked one of the transmembrane domains and showed a slight developmental delay in homozygous Drosophila larvae. Like mutations in a number of other HSP hairpin proteins, this lesion is homozygous viable, and further characterization of its phenotype will help elucidate how Arl6IP1 contributes to modeling the axonal ER network. In conclusion, my work shows the utility of GFP markers of axonal ER, it can facilitate faster screening for other genes that potentially regulate ER structure and for ageing phenotypes that are not apparent in larval stages, and suggests Arl6IP1 as another HSP protein with a role in axonal ER organization.

Subjects/Keywords: Axonal ER; neurodegeneration; drosophila

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APA (6^th Edition):

Sohail, A. (2019). Visualizing Roles of Spastic Paraplegia Proteins in Organizing Axonal ER in Live Drosophila . (Thesis). University of Cambridge. Retrieved from https://www.repository.cam.ac.uk/handle/1810/290113

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):

Sohail, Anood. “Visualizing Roles of Spastic Paraplegia Proteins in Organizing Axonal ER in Live Drosophila .” 2019. Thesis, University of Cambridge. Accessed July 22, 2019. https://www.repository.cam.ac.uk/handle/1810/290113.

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

MLA Handbook (7^th Edition):

Sohail, Anood. “Visualizing Roles of Spastic Paraplegia Proteins in Organizing Axonal ER in Live Drosophila .” 2019. Web. 22 Jul 2019.

Vancouver:

Sohail A. Visualizing Roles of Spastic Paraplegia Proteins in Organizing Axonal ER in Live Drosophila . [Internet] [Thesis]. University of Cambridge; 2019. [cited 2019 Jul 22]. Available from: https://www.repository.cam.ac.uk/handle/1810/290113.

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

Council of Science Editors:

Sohail A. Visualizing Roles of Spastic Paraplegia Proteins in Organizing Axonal ER in Live Drosophila . [Thesis]. University of Cambridge; 2019. Available from: https://www.repository.cam.ac.uk/handle/1810/290113

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

University of Cambridge

12. Levy, Daniel Robert Siegfried. Exploring the role of Leucine Rich Repeat Kinase 2 within the innate immune system .

Degree: 2018, University of Cambridge

URL: https://www.repository.cam.ac.uk/handle/1810/273736

► Leucine rich repeat kinase 2 (LRRK2) is a 286 kDa protein expressed in a variety of tissues and cell types, including neuronal tissue and innate… (more)

▼ Leucine rich repeat kinase 2 (LRRK2) is a 286 kDa protein expressed in a variety of tissues and cell types, including neuronal tissue and innate immune cells. Mutations in LRRK2 have been linked to inflammatory diseases, most notably Crohn’s disease and Parkinson’s disease. Further to this, LRRK2 expression is induced by innate immune stimuli, and can be phosphorylated by Myd88 directed TLR signalling. Functional experiments were performed using macrophages from WT and LRRK2 knockout mice. Many phenotypes and interactions have been described for LRRK2 in a neuronal or in vitro context; therefore experiments in macrophages were specifically designed to investigate these phenotypes and interactions in an innate immune context. LRRK2 interacts with a range of small GTPase proteins called Rabs, which coordinate and carry out vesicular trafficking, including that of innate immune receptors. Further interactions have been shown with clathrin-mediated endocytic machinery and phagocytic machinery; including cytoskeletal components actin and tubulin. Accordingly, the role of LRRK2 in the expression, membrane localisation, and ligand-induced endocytosis of the innate immune receptors such as TLR4 were assayed. TLR4 plays an important role in immune responses to alpha-synuclein, an immunogenic protein aggregate that accumulates as part of Parkinson’s disease pathology, making it a particularly interesting target for this assay. No effect was shown for LRRK2 on TLR4 expression or receptor mediated endocytosis, so attention was focused upon LRRK2 cytoskeletal interactions. An unclear role of LRRK2 has been described in phagocytosis. Application of LRRK2 KO macrophages in a series of systematic phagocytosis assays was used to demonstrate and clarify that there is no role of LRRK2 in the phagocytosis of simple beads, opsonised material, or complex bacterial targets expressing a range of immunogenic molecules such as LPS. A genome wide approach was applied to further investigate the role of LRRK2 in TLR4 mediated signalling, as well as NOD2 mediated signalling. Comparison of LPS responses between WT and LRRK2 KO genotype macrophages identified a role of LRRK2 in modulating transcription of a range of chemokines and chemokine receptors. This indicates a specific role of LRRK2 in regulating chemotaxis in LPS stimulated cells. Knockout of LRRK2 resulted in a complete reversal of the regulation of the expression of EPAC1, a cAMP inducible protein working in parallel with a previously described LRRK2 interacting protein PKA. EPAC1 acts, at least in part, via Ca2+ signalling. Modulation of signalling through pathways such as Ca2+, Wnt and cAMP appear as a theme in results described in this transcriptomic experiment. A parallel metabolomic approach allowed analysis of ceramide levels in resting and innate immune stimulated macrophages. Ceramides are lipid molecules able to activate the NLRP3 inflammasome, as well as modulate alpha-synuclein pathology via ceramide metabolomic products. In contrast to results described in neuronal…

Subjects/Keywords: immunology; Parkinson's disease; neurodegeneration

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APA (6^th Edition):

Levy, D. R. S. (2018). Exploring the role of Leucine Rich Repeat Kinase 2 within the innate immune system . (Thesis). University of Cambridge. Retrieved from https://www.repository.cam.ac.uk/handle/1810/273736

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):

Levy, Daniel Robert Siegfried. “Exploring the role of Leucine Rich Repeat Kinase 2 within the innate immune system .” 2018. Thesis, University of Cambridge. Accessed July 22, 2019. https://www.repository.cam.ac.uk/handle/1810/273736.

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

MLA Handbook (7^th Edition):

Levy, Daniel Robert Siegfried. “Exploring the role of Leucine Rich Repeat Kinase 2 within the innate immune system .” 2018. Web. 22 Jul 2019.

Vancouver:

Levy DRS. Exploring the role of Leucine Rich Repeat Kinase 2 within the innate immune system . [Internet] [Thesis]. University of Cambridge; 2018. [cited 2019 Jul 22]. Available from: https://www.repository.cam.ac.uk/handle/1810/273736.

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

Council of Science Editors:

Levy DRS. Exploring the role of Leucine Rich Repeat Kinase 2 within the innate immune system . [Thesis]. University of Cambridge; 2018. Available from: https://www.repository.cam.ac.uk/handle/1810/273736

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

Vanderbilt University

13. Ward, Nicholas John. The Transient Receptor Potential Vanilloid-1 Channel and Neuronal Survival in Degenerative Disease.

Degree: PhD, Neuroscience, 2014, Vanderbilt University

URL: http://etd.library.vanderbilt.edu/available/etd-07212014-152449/ ;

► Neuronal responses to stress are an important component of neurodegenerative disease and may represent targets for therapeutic intervention. In normal and pathogenic physiological conditions, members… (more)

Subjects/Keywords: neurodegeneration; glaucoma; TRPV1; TRP channels

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APA (6^th Edition):

Ward, N. J. (2014). The Transient Receptor Potential Vanilloid-1 Channel and Neuronal Survival in Degenerative Disease. (Doctoral Dissertation). Vanderbilt University. Retrieved from http://etd.library.vanderbilt.edu/available/etd-07212014-152449/ ;

Chicago Manual of Style (16^th Edition):

Ward, Nicholas John. “The Transient Receptor Potential Vanilloid-1 Channel and Neuronal Survival in Degenerative Disease.” 2014. Doctoral Dissertation, Vanderbilt University. Accessed July 22, 2019. http://etd.library.vanderbilt.edu/available/etd-07212014-152449/ ;.

MLA Handbook (7^th Edition):

Ward, Nicholas John. “The Transient Receptor Potential Vanilloid-1 Channel and Neuronal Survival in Degenerative Disease.” 2014. Web. 22 Jul 2019.

Vancouver:

Ward NJ. The Transient Receptor Potential Vanilloid-1 Channel and Neuronal Survival in Degenerative Disease. [Internet] [Doctoral dissertation]. Vanderbilt University; 2014. [cited 2019 Jul 22]. Available from: http://etd.library.vanderbilt.edu/available/etd-07212014-152449/ ;.

Council of Science Editors:

Ward NJ. The Transient Receptor Potential Vanilloid-1 Channel and Neuronal Survival in Degenerative Disease. [Doctoral Dissertation]. Vanderbilt University; 2014. Available from: http://etd.library.vanderbilt.edu/available/etd-07212014-152449/ ;

University of New South Wales

14. Chiu, Alexander Simon Che-Kean. A toxicological analysis of the cyanotoxin β-methylamino-L-alanine at multiple neural levels and identification of novel modes of activity.

Degree: Biotechnology & Biomolecular Sciences, 2013, University of New South Wales

URL: http://handle.unsw.edu.au/1959.4/52422 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:11095/SOURCE01?view=true

► The cyanotoxin β-methylamino-L-alanine (BMAA) has long been associated with the elevated incidence of amyotrophic lateral sclerosis/Parkinsonism dementia complex (ALS/PDC). BMAA has been shown to be… (more)

▼ The cyanotoxin β-methylamino-L-alanine (BMAA) has long been associated with the elevated incidence of amyotrophic lateral sclerosis/Parkinsonism dementia complex (ALS/PDC). BMAA has been shown to be produced across the cyanobacterial order and its detection has been reported in a variety of aquatic and terrestrial environments worldwide, suggesting that it is ubiquitous. Various in vivo studies on rats, mice, chicks, monkeys and zebrafish have shown that BMAA can cause neurodegenerative symptoms such as ataxia and convulsions, as well as disruption to neural development. Previous in vitro studies using mice, rats and leeches have shown that BMAA acts predominantly on motor neurons. Observed increases in the generation of reactive oxygen species (ROS) and Ca2+ influx, coupled with disruption to mitochondrial activity and general neuronal death, indicate that the main mode of activity is via excitotoxic mechanisms. Data presented here indicate that BMAA induces increased intracellular Ca2+ influx, DNA damage, mitochondrial activity, lactate dehydrogenase (LDH) release and generation of ROS in human neurons. The amelioration of LDH release in the presence of the N methyl-D-aspartate (NMDA) receptor antagonist MK801 indicates that the neurotoxic effects of BMAA are mediated via NMDA receptor activation. Immunocytochemical stains show that BMAA induces the expression of neuronal nitric oxide synthase (nNOS) and caspase-3 indicating that it can stimulate apoptosis in human neurons, presumably via activation of NMDA receptors. Rat olfactory ensheathing cells (OECs) were also challenged with exogenous BMAA resulting in elevated cell death. Significant increases in Ca2+ influx, enhanced production of ROS, and disruption to mitochondrial activity were observed in OECs. This is the first study investigating BMAA toxicity using pure glial cells. These findings align BMAA with all proposed mechanisms of degeneration in ALS, those being non-cell autonomous death, excitotoxicity and mitochondrial dysfunction. Additionally, novel genes and proteins have been identified that were differentially expressed in BMAA treated OECs. Some of the identified genes/proteins of interest have previously been linked to Alzheimer's disease. Other genes/proteins identified have reported functions in the regulation of mitochondrial activity and cell cycle and apoptosis. Cell cycle analysis of OECs treated with BMAA resulted in cell cycle arrest at the G2/M phase. Advisors/Committee Members: Neilan, Brett, Biotechnology & Biomolecular Sciences, Faculty of Science, UNSW, Welch, Jeffrey, Biotechnology & Biomolecular Sciences, Faculty of Science, UNSW.

Subjects/Keywords: ALS/PDC; BMAA; Neurodegeneration; Cyanotoxin

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APA (6^th Edition):

Chiu, A. S. C. (2013). A toxicological analysis of the cyanotoxin β-methylamino-L-alanine at multiple neural levels and identification of novel modes of activity. (Doctoral Dissertation). University of New South Wales. Retrieved from http://handle.unsw.edu.au/1959.4/52422 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:11095/SOURCE01?view=true

Chicago Manual of Style (16^th Edition):

Chiu, Alexander Simon Che-Kean. “A toxicological analysis of the cyanotoxin β-methylamino-L-alanine at multiple neural levels and identification of novel modes of activity.” 2013. Doctoral Dissertation, University of New South Wales. Accessed July 22, 2019. http://handle.unsw.edu.au/1959.4/52422 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:11095/SOURCE01?view=true.

MLA Handbook (7^th Edition):

Chiu, Alexander Simon Che-Kean. “A toxicological analysis of the cyanotoxin β-methylamino-L-alanine at multiple neural levels and identification of novel modes of activity.” 2013. Web. 22 Jul 2019.

Vancouver:

Chiu ASC. A toxicological analysis of the cyanotoxin β-methylamino-L-alanine at multiple neural levels and identification of novel modes of activity. [Internet] [Doctoral dissertation]. University of New South Wales; 2013. [cited 2019 Jul 22]. Available from: http://handle.unsw.edu.au/1959.4/52422 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:11095/SOURCE01?view=true.

Council of Science Editors:

Chiu ASC. A toxicological analysis of the cyanotoxin β-methylamino-L-alanine at multiple neural levels and identification of novel modes of activity. [Doctoral Dissertation]. University of New South Wales; 2013. Available from: http://handle.unsw.edu.au/1959.4/52422 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:11095/SOURCE01?view=true

University of Minnesota

15. Amar, Fatou. Cellular And Molecular Mechanism Of Action Of The Amyloid-Beta Oligomer Abeta Star 56.

Degree: PhD, Neuroscience, 2016, University of Minnesota

URL: http://hdl.handle.net/11299/178973

► Alzheimer’s disease (AD) is a progressive neurodegenerative disorder, with asymptomatic and symptomatic phases. Hallmark lesions of AD include extracellular deposits of fibrillar amyloid-β (A β)… (more)

Subjects/Keywords: Alzheimer's disease; molecular neuroscience; neurodegeneration

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APA (6^th Edition):

Amar, F. (2016). Cellular And Molecular Mechanism Of Action Of The Amyloid-Beta Oligomer Abeta Star 56. (Doctoral Dissertation). University of Minnesota. Retrieved from http://hdl.handle.net/11299/178973

Chicago Manual of Style (16^th Edition):

Amar, Fatou. “Cellular And Molecular Mechanism Of Action Of The Amyloid-Beta Oligomer Abeta Star 56.” 2016. Doctoral Dissertation, University of Minnesota. Accessed July 22, 2019. http://hdl.handle.net/11299/178973.

MLA Handbook (7^th Edition):

Amar, Fatou. “Cellular And Molecular Mechanism Of Action Of The Amyloid-Beta Oligomer Abeta Star 56.” 2016. Web. 22 Jul 2019.

Vancouver:

Amar F. Cellular And Molecular Mechanism Of Action Of The Amyloid-Beta Oligomer Abeta Star 56. [Internet] [Doctoral dissertation]. University of Minnesota; 2016. [cited 2019 Jul 22]. Available from: http://hdl.handle.net/11299/178973.

Council of Science Editors:

Amar F. Cellular And Molecular Mechanism Of Action Of The Amyloid-Beta Oligomer Abeta Star 56. [Doctoral Dissertation]. University of Minnesota; 2016. Available from: http://hdl.handle.net/11299/178973

University of Pennsylvania

16. Covy, Jason P. The Pathological and Biochemical Characterization of Leucine-Rich Repeat Kinase 2 in Parkinson’s Disease.

Degree: 2010, University of Pennsylvania

URL: https://repository.upenn.edu/edissertations/1553

► Parkinson's disease (PD) is a debilitating and progressive neurodegenerative disorder that affects over 6 million people worldwide. Despite being the most common movement disorder in… (more)

▼ Parkinson's disease (PD) is a debilitating and progressive neurodegenerative disorder that affects over 6 million people worldwide. Despite being the most common movement disorder in the U.S., there is still no effective treatment for halting the progression of disease. While generally considered a sporadic and idiopathic disorder, a number of mutations in genetic loci causal for PD have provided valuable insight into the etiology of disease. Mutations in the gene for leucine-rich repeat kinase 2 (LRRK2) are the single most common cause of both familial and sporadic forms of PD. LRRK2 is a large 2527‐amino acid protein with several distinct domains: leucine-rich repeats, Ras-like GTPase domain, C-terminal of ROC (COR) domain, serine/threonine kinase domain, and WD40 repeats; however the understanding of LRRK2 function or how its aberration may lead to disease is still rudimentary. In 2006, we identified and characterized 3 patients with the G2019S LRRK2 mutation; however this search was limited to a few sequenced exons. An expanded screen identified 2 new patients with LRRK2 mutation, and the clinical and neuropathological findings for all these patients are provided herein. A novel system to express and purify the full-length protein with active in-vitro kinase activity revealed that the most common disease causing alteration (G2019S) markedly increases kinase activity. This highlighted overactive kinase activity as a possible intervention point for its aberrant effects. Screening for molecular inhibitors of kinase activity identified several compounds (Gö6976, K252a, and staurosporine) that share a basic indolocarbazole structure, which act as potent inhibitors of LRRK2 at low nanomolar concentrations. Increased kinase activity in the absence of outside factors is unlikely to account for the pathogenicity of the G2019S mutation. A more careful analysis of LRRK2 kinase activity revealed that this mutation, relative to the wildtype and other pathogenic mutations, may act in a novel pathway leading to disease by disrupting LRRK2 sensitivity to manganese kinase inhibition. Furthermore, based on kinetic data, we propose a novel hypothesis that LRRK2 may act as a cellular sensor of manganese levels, and disruption of this function may contribute to disease.

Subjects/Keywords: LRRK2; Parkinson's disease; neurodegeneration; Neurosciences

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APA (6^th Edition):

Covy, J. P. (2010). The Pathological and Biochemical Characterization of Leucine-Rich Repeat Kinase 2 in Parkinson’s Disease. (Thesis). University of Pennsylvania. Retrieved from https://repository.upenn.edu/edissertations/1553

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):

Covy, Jason P. “The Pathological and Biochemical Characterization of Leucine-Rich Repeat Kinase 2 in Parkinson’s Disease.” 2010. Thesis, University of Pennsylvania. Accessed July 22, 2019. https://repository.upenn.edu/edissertations/1553.

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

MLA Handbook (7^th Edition):

Covy, Jason P. “The Pathological and Biochemical Characterization of Leucine-Rich Repeat Kinase 2 in Parkinson’s Disease.” 2010. Web. 22 Jul 2019.

Vancouver:

Covy JP. The Pathological and Biochemical Characterization of Leucine-Rich Repeat Kinase 2 in Parkinson’s Disease. [Internet] [Thesis]. University of Pennsylvania; 2010. [cited 2019 Jul 22]. Available from: https://repository.upenn.edu/edissertations/1553.

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

Council of Science Editors:

Covy JP. The Pathological and Biochemical Characterization of Leucine-Rich Repeat Kinase 2 in Parkinson’s Disease. [Thesis]. University of Pennsylvania; 2010. Available from: https://repository.upenn.edu/edissertations/1553

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

University of New South Wales

17. Braidy, Nady. NAD+ metabolism in neurodegeneration and aging.

Degree: Medical Sciences, 2011, University of New South Wales

URL: http://handle.unsw.edu.au/1959.4/51345 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:10026/SOURCE02?view=true

► Elevated levels of several kynurenine pathway (KP) metabolites, e.g. quinolinic acid (QUIN), have been implicated in the aetiology of several neurodegenerative diseases such as Alzheimer‟s… (more)

▼ Elevated levels of several kynurenine pathway (KP) metabolites, e.g. quinolinic acid (QUIN), have been implicated in the aetiology of several neurodegenerative diseases such as Alzheimer‟s disease (AD) and Multiple Sclerosis (MS). The end product of the KP is NAD+, an essential cofactor for energy metabolism. NAD+ also serves as the sole substrate for the DNA repair enzyme, poly(ADP-ribose) polymerase (PARP). More recently, NAD+ has been identified as an essential substrate for a new class of histone deacetylases known as SIRT1, which has been linked to longevity. Free radical mediated PARP activation and NAD+ depletion may contribute to brain aging and tissue damage in multiple brain disorders.Our results indicate a direct involvement of the KP in NAD+ synthesis in human brain cells, and that reduced intracellular NAD+ synthesis leads to reduced activity of NAD+ dependent histone deacetylase function. We show that the KP metabolite and NMDA receptor agonist, QUIN is a substrate of NAD+ synthesis in nanomolar concentrations in both astrocytes and neurons but is cytotoxic at higher amounts in both cell types. These results also show a clear neuroprotective effect of NMDA receptor antagonism and nitric oxide synthase inhibition against QUIN mediated neuronal and glial cytoxicity, strongly suggesting that QUIN-induced excitotoxicity in astrocytes and neurons is mediated by overactivation of the NMDA receptor. We also show that natural polyphenolic compounds can attenuate QUIN-mediated neurotoxicity by a number of mechanisms reported herein.We also provide evidence for the first time that tryptophan metabolism leading to NAD+ synthesis is unregulated in tissue obtained from aged female wistar rats. SIRT1 activity was also decreased and acetylated p53 increased in these same animals in response to an unregulated PARP-mediated NAD+ depletion. Consistent with these animal data we also found that human serum NAD+ levels are reduced in MS. Advisors/Committee Members: Grant, Ross, Medical Sciences, Faculty of Medicine, UNSW, Guillemin, Gilles, Medical Sciences, Faculty of Medicine, UNSW.

Subjects/Keywords: NAD+; metabolism; neurodegeneration; aging

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APA (6^th Edition):

Braidy, N. (2011). NAD+ metabolism in neurodegeneration and aging. (Doctoral Dissertation). University of New South Wales. Retrieved from http://handle.unsw.edu.au/1959.4/51345 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:10026/SOURCE02?view=true

Chicago Manual of Style (16^th Edition):

Braidy, Nady. “NAD+ metabolism in neurodegeneration and aging.” 2011. Doctoral Dissertation, University of New South Wales. Accessed July 22, 2019. http://handle.unsw.edu.au/1959.4/51345 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:10026/SOURCE02?view=true.

MLA Handbook (7^th Edition):

Braidy, Nady. “NAD+ metabolism in neurodegeneration and aging.” 2011. Web. 22 Jul 2019.

Vancouver:

Braidy N. NAD+ metabolism in neurodegeneration and aging. [Internet] [Doctoral dissertation]. University of New South Wales; 2011. [cited 2019 Jul 22]. Available from: http://handle.unsw.edu.au/1959.4/51345 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:10026/SOURCE02?view=true.

Council of Science Editors:

Braidy N. NAD+ metabolism in neurodegeneration and aging. [Doctoral Dissertation]. University of New South Wales; 2011. Available from: http://handle.unsw.edu.au/1959.4/51345 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:10026/SOURCE02?view=true

University of Manitoba

18. Acosta, Crystal May R. Antigenic induction of nerve growth factor (NGF) in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS).

Degree: Pharmacy, 2013, University of Manitoba

URL: http://hdl.handle.net/1993/23504

► Nerve growth factor (NGF) represents a new therapeutic strategy for multiple sclerosis (MS) because of its immunomodulatory and neuroprotective activity. To analyze changes in NGF… (more)

Subjects/Keywords: MS; NGF; Neurodegeneration; Neuroimmunology

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APA (6^th Edition):

Acosta, C. M. R. (2013). Antigenic induction of nerve growth factor (NGF) in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). (Masters Thesis). University of Manitoba. Retrieved from http://hdl.handle.net/1993/23504

Chicago Manual of Style (16^th Edition):

Acosta, Crystal May R. “Antigenic induction of nerve growth factor (NGF) in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS).” 2013. Masters Thesis, University of Manitoba. Accessed July 22, 2019. http://hdl.handle.net/1993/23504.

MLA Handbook (7^th Edition):

Acosta, Crystal May R. “Antigenic induction of nerve growth factor (NGF) in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS).” 2013. Web. 22 Jul 2019.

Vancouver:

Acosta CMR. Antigenic induction of nerve growth factor (NGF) in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). [Internet] [Masters thesis]. University of Manitoba; 2013. [cited 2019 Jul 22]. Available from: http://hdl.handle.net/1993/23504.

Council of Science Editors:

Acosta CMR. Antigenic induction of nerve growth factor (NGF) in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). [Masters Thesis]. University of Manitoba; 2013. Available from: http://hdl.handle.net/1993/23504

University of Missouri – Columbia

19. Pinnegar, Abbie Jolene. Investigating canine degenerative myelopathy as a disease model of amyotrophic lateral sclerosis for histopathological evidence of dysphagia.

Degree: 2012, University of Missouri – Columbia

URL: http://hdl.handle.net/10355/35437

► [ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Unspecified swallowing impairment (dysphagia) was recently reported in dogs with degenerative myelopathy (DM), a proposed… (more)

Subjects/Keywords: dysphagia; brainstem nuclei; neurodegeneration

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APA (6^th Edition):

Pinnegar, A. J. (2012). Investigating canine degenerative myelopathy as a disease model of amyotrophic lateral sclerosis for histopathological evidence of dysphagia. (Thesis). University of Missouri – Columbia. Retrieved from http://hdl.handle.net/10355/35437

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):

Pinnegar, Abbie Jolene. “Investigating canine degenerative myelopathy as a disease model of amyotrophic lateral sclerosis for histopathological evidence of dysphagia.” 2012. Thesis, University of Missouri – Columbia. Accessed July 22, 2019. http://hdl.handle.net/10355/35437.

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

MLA Handbook (7^th Edition):

Pinnegar, Abbie Jolene. “Investigating canine degenerative myelopathy as a disease model of amyotrophic lateral sclerosis for histopathological evidence of dysphagia.” 2012. Web. 22 Jul 2019.

Vancouver:

Pinnegar AJ. Investigating canine degenerative myelopathy as a disease model of amyotrophic lateral sclerosis for histopathological evidence of dysphagia. [Internet] [Thesis]. University of Missouri – Columbia; 2012. [cited 2019 Jul 22]. Available from: http://hdl.handle.net/10355/35437.

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

Council of Science Editors:

Pinnegar AJ. Investigating canine degenerative myelopathy as a disease model of amyotrophic lateral sclerosis for histopathological evidence of dysphagia. [Thesis]. University of Missouri – Columbia; 2012. Available from: http://hdl.handle.net/10355/35437

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

Boston University

20. Bleiberg, Benjamin Aaron. Evaluating the concordance of N-terminal and full length Huntington's disease modifiers and identifying potential therapeutic targets in Drosophila.

Degree: MS, Medical Sciences, 2016, Boston University

URL: http://hdl.handle.net/2144/16770

► Huntington’s disease (HD) is one of nine polyglutamine diseases and it is caused by a CAG expansion in the HTT gene. HD is an autosomal,… (more)

▼ Huntington’s disease (HD) is one of nine polyglutamine diseases and it is caused by a CAG expansion in the HTT gene. HD is an autosomal, dominantly inherited neurodegenerative disease affecting between 2 and 5 individuals per 100,000 worldwide and it is currently untreatable. HD spreads from the striatum to the rest of the brain and causes widespread motor, cognitive, and psychiatric symptoms, including Huntington’s chorea. A fruitful approach to identifying potential therapeutic targets for HD is to modify genes in a model organism in an unbiased manner and screen the effect by testing the model in a functional assay. Drosophila models of HD have emerged as key tools for these large scale genetic screens thanks to their combination of ease of maintenance, and breeding in large numbers and their ability to be tested neurobehaviorally. During the course of HD pathogenesis in mammals, the FL-HTT protein is cleaved by many proteases including caspase-6. This cleavage leads to the co-existence of N-terminal (NT) as well as full-length (FL) forms of mutant HTT in the HD neurons. Drosophila lacks caspase-6 therefore FL-HTT is not naturally cleaved at its target site, this allows us to express either the FL mutant HTT or its cleaved NT fragment independently to characterize their differential pathogenic contribution. This study aims to test the concordance of a sample of 75 NT-HTT modifiers identified through a directed screen by testing them in a FL-HTT model. In doing so, we hope to identify shared modifiers and shared functional genetic networks, which may be particularly central to HD progression and useful areas in which to discover therapeutic targets. Further, this study may help to determine what types of models are necessary for future screens to adequately understand the genetic networks that underpin HD progression. In order to assess the impact of the modifier, flies expressing both the modifier and FL-HTT were tested in a climbing assay that measures motor function taking advantage of the model’s innate negative geotactic behavior. Motor performance is measured as the percentage of flies of each genotype that climb up to a 9 cm threshold in a given time interval. Flies were tested at 6 time points on days 18, 19, 20, 21, 22, and 25 of age in order to observe their level of neurobehavioral function in comparison to a positive control of flies with FL-HTT and no modifier and a negative control of flies without mutant HTT. When NT modifiers were tested in the FL model, there was an enrichment in modifiers relative to what is seen by chance. The NT suppressor sample was significantly enriched in modifier genes that effected motor performance in the FL model. Meanwhile, NT HD enhancers were not enriched with modifiers in the FL model. Some modifiers demonstrated contradictory effects on motor performance depending on the HD model tested. This could be caused by different mechanisms of toxicity inherent to NT versus FL HD or from secondary toxicity as the FL experiment occurred over a longer time period…

Subjects/Keywords: Medicine; Drosophila; Neurodegeneration; Huntington's disease

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APA (6^th Edition):

Bleiberg, B. A. (2016). Evaluating the concordance of N-terminal and full length Huntington's disease modifiers and identifying potential therapeutic targets in Drosophila. (Masters Thesis). Boston University. Retrieved from http://hdl.handle.net/2144/16770

Chicago Manual of Style (16^th Edition):

Bleiberg, Benjamin Aaron. “Evaluating the concordance of N-terminal and full length Huntington's disease modifiers and identifying potential therapeutic targets in Drosophila.” 2016. Masters Thesis, Boston University. Accessed July 22, 2019. http://hdl.handle.net/2144/16770.

MLA Handbook (7^th Edition):

Bleiberg, Benjamin Aaron. “Evaluating the concordance of N-terminal and full length Huntington's disease modifiers and identifying potential therapeutic targets in Drosophila.” 2016. Web. 22 Jul 2019.

Vancouver:

Bleiberg BA. Evaluating the concordance of N-terminal and full length Huntington's disease modifiers and identifying potential therapeutic targets in Drosophila. [Internet] [Masters thesis]. Boston University; 2016. [cited 2019 Jul 22]. Available from: http://hdl.handle.net/2144/16770.

Council of Science Editors:

Bleiberg BA. Evaluating the concordance of N-terminal and full length Huntington's disease modifiers and identifying potential therapeutic targets in Drosophila. [Masters Thesis]. Boston University; 2016. Available from: http://hdl.handle.net/2144/16770

21. Catalano, Carmen. Correlazioni molecolari fra angiogenesi e neurodegenerazione.

Degree: 2013, Università degli Studi di Catania

URL: http://hdl.handle.net/10761/1321

Studio e valutazione dei potenziali effetti del farmaco immunomodulante lenalidomide nelle patologie neurodegenerative.

Subjects/Keywords: Area 05 - Scienze biologiche; lenalidomide, angiogenesis, neurodegeneration

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APA (6^th Edition):

Catalano, C. (2013). Correlazioni molecolari fra angiogenesi e neurodegenerazione. (Thesis). Università degli Studi di Catania. Retrieved from http://hdl.handle.net/10761/1321

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):

Catalano, Carmen. “Correlazioni molecolari fra angiogenesi e neurodegenerazione.” 2013. Thesis, Università degli Studi di Catania. Accessed July 22, 2019. http://hdl.handle.net/10761/1321.

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

MLA Handbook (7^th Edition):

Catalano, Carmen. “Correlazioni molecolari fra angiogenesi e neurodegenerazione.” 2013. Web. 22 Jul 2019.

Vancouver:

Catalano C. Correlazioni molecolari fra angiogenesi e neurodegenerazione. [Internet] [Thesis]. Università degli Studi di Catania; 2013. [cited 2019 Jul 22]. Available from: http://hdl.handle.net/10761/1321.

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

Council of Science Editors:

Catalano C. Correlazioni molecolari fra angiogenesi e neurodegenerazione. [Thesis]. Università degli Studi di Catania; 2013. Available from: http://hdl.handle.net/10761/1321

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

Texas A&M University

22. Huang, Pei-San. Effects of Chronic Nicotine Exposure and Lack of High Affinity Nicotinic Receptors on Cortico-Hippocampal Areas in the Aging Mouse Brain.

Degree: 2012, Texas A&M University

URL: http://hdl.handle.net/1969.1/ETD-TAMU-2012-05-11067

► Nicotine, the major psychoactive ingredient of tobacco smoke, underlies numerous effects by activating neuronal nicotinic acetylcholine receptors. Both in vitro and in vivo studies suggest… (more)

▼ Nicotine, the major psychoactive ingredient of tobacco smoke, underlies numerous effects by activating neuronal nicotinic acetylcholine receptors. Both in vitro and in vivo studies suggest that nicotine is neuroprotective and improves cognitive performance. Epidemiology studies show that smoking is negatively correlated with the incidence of Parkinson's disease and Alzheimer's disease. Postmortem research and neuroimaging studies show that loss of nicotinic binding sites in the brain is the major feature of neurodegenerative diseases related to dementia and cognitive impairment. Caloric restriction, a regimen that extends the lifespan in all mammalian species studied so far including rodents and primates, is a highly regulated response to food deprivation. It is believed that the longevity effect of caloric restriction is mediated by SIRT1, a NAD-dependent deacetylase, and its related genes. Nicotine's effect on body weight could also lead to weight loss by decreasing caloric absorption consumption. The goal of this study was to find the possible correlation between nicotine's effects and the activation of SIRT1 and its related genes. Using beta2-/- mice that lack high affinity beta2 nicotinic acetylcholine receptors (nAChRs), we first demonstrated that beta2* nAChRs do not directly regulate expression of survival genes. However, we found that loss of beta2* nAChRs could result in augmented cellular stress, which indirectly increased expression of SIRT1, Nampt, and Ku70, possibly as an adaptive response to provide protection against neurodegeneration. We also found that loss of endogenous activation of beta2* nAChRs had less effect on synaptic connections but strongly impaired survival of hippocampal GABAergic neurons. To activate beta2* nAChRs in normal mice, we administered nicotine through drinking water. In a short-term exposure study, we determined the dose of nicotine to be used in young adult mice, and found that chronic nicotine treatment was anxiolytic, decreased caloric consumption, increased nAChR binding sites, and most importantly, increased expression of SIRT1 and its related genes. Finally, we compared long-term nicotine treatment with caloric restriction in middle-aged mice to examine their effects to brain aging, and our results indicated that in mice long term caloric restriction and nicotine treatment both tend to improve memory in aging mice, but appear to act through different mechanisms. Advisors/Committee Members: Winzer-Serhan, Ursula H. (advisor), Abbott, Louise C. (advisor), Welsh, C. Jane (committee member), Griffith, William H. (committee member).

Subjects/Keywords: nicotine; neuroprotection; aging; nAChRs; neurodegeneration; caloric restriction

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APA (6^th Edition):

Huang, P. (2012). Effects of Chronic Nicotine Exposure and Lack of High Affinity Nicotinic Receptors on Cortico-Hippocampal Areas in the Aging Mouse Brain. (Thesis). Texas A&M University. Retrieved from http://hdl.handle.net/1969.1/ETD-TAMU-2012-05-11067

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):

Huang, Pei-San. “Effects of Chronic Nicotine Exposure and Lack of High Affinity Nicotinic Receptors on Cortico-Hippocampal Areas in the Aging Mouse Brain.” 2012. Thesis, Texas A&M University. Accessed July 22, 2019. http://hdl.handle.net/1969.1/ETD-TAMU-2012-05-11067.

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

MLA Handbook (7^th Edition):

Huang, Pei-San. “Effects of Chronic Nicotine Exposure and Lack of High Affinity Nicotinic Receptors on Cortico-Hippocampal Areas in the Aging Mouse Brain.” 2012. Web. 22 Jul 2019.

Vancouver:

Huang P. Effects of Chronic Nicotine Exposure and Lack of High Affinity Nicotinic Receptors on Cortico-Hippocampal Areas in the Aging Mouse Brain. [Internet] [Thesis]. Texas A&M University; 2012. [cited 2019 Jul 22]. Available from: http://hdl.handle.net/1969.1/ETD-TAMU-2012-05-11067.

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

Council of Science Editors:

Huang P. Effects of Chronic Nicotine Exposure and Lack of High Affinity Nicotinic Receptors on Cortico-Hippocampal Areas in the Aging Mouse Brain. [Thesis]. Texas A&M University; 2012. Available from: http://hdl.handle.net/1969.1/ETD-TAMU-2012-05-11067

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

Wright State University

23. Davidson, Molly Elizabeth. Neurodegeneration and Neuroinflammation in a Mouse Model of Sarin Exposure.

Degree: MS, Pharmacology and Toxicology, 2007, Wright State University

URL: http://rave.ohiolink.edu/etdc/view?acc_num=wright1189715827

► Sarin is an organophosphorus (OP) ester chemical warfare agent (CWA) that has been used in past terrorist attacks. It remains a threat today because of… (more)

▼ Sarin is an organophosphorus (OP) ester chemical warfare agent (CWA) that has been used in past terrorist attacks. It remains a threat today because of its ease of manufacture and dispersal. Sarin acts by irreversibly inactivating acetylcholinesterase and interfering with neurotransmission by allowing acetylcholine to build up at neuro-effector junctions, where it continuously elicits a response. Symptoms of sarin toxicity include seizures, hypersecretions, respiratory distress and death in extreme cases. Previous studies on OP poisoning indicate that sarin exposure causes neurodegeneration and neuroinflammation in conjunction with seizure activity. In order to determine the mode of neuronal death and the extent of neuroinflammation induced by sarin exposure, C57Bl/6J mice were first dosed s.c. with 1.5 mg/kg cresylbenzodioxaphosphorin oxide (CBDP) to inhibit the large amount of carboxylesterase found in rodents. One hour later, mice were dosed with 24 ug/kg sarin, a dose which produces approximately 17% lethality. One group of mice was also dosed with 1.7 mg/kg 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), a 5-HT1A receptor agonist, which has been shown by others to decrease different types of neuronal injury. Mice were sacrificed at times ranging from four hours to ten days after sarin administration and left or right brain hemispheres were collected and frozen in isopentane for histological examination. To detect DNA fragmentation, 10um-thick sections were TUNEL-stained using the NeuroTACS II in situ apoptosis detection kit. Activated caspase-3 and interleukin-1beta (IL-1beta) were detected by immunohistochemistry to determine whether apoptotic cell death and neuroinflammation were occurring. Manual cell counts were performed on micrographs of dentate gyrus and CA1 regions of hippocampus, amygdala and piriform cortex in NIH Image. Statistically significant TUNEL labeling was observed at various time points in all brain regions except CA1 hippocampus. Significant increases in caspase-3 staining were observed only in piriform cortex and CA1 hippocampus at 24 hours and four days post-sarin injection, respectively. IL-1beta expression was significantly increased in CA1 hippocampus at four days after sarin injection and in all brain regions except piriform cortex at ten days after sarin exposure. Neither TUNEL nor caspase-3 labeling were significantly decreased with 8-OH-DPAT treatment. The amygdala and dentate gyrus regions showed significant decreases in IL-1beta expression after 8-OH-DPAT treatment. Statistically non-significant upward trends over time in TUNEL labeling and IL-1beta expression were observed. In contrast, caspase-3 expression exhibited a gradual, non-significant decrease at later time points. These trends may be indicative of a decreasing role played by apoptotic cell death and an increasing or persisting role for oncotic cell death and inflammation in sarin neurotoxicity. Advisors/Committee Members: Cool, David (Advisor).

Subjects/Keywords: Health Sciences, Toxicology; sarin; organophosphate; neuroinflammation; neurodegeneration

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APA (6^th Edition):

Davidson, M. E. (2007). Neurodegeneration and Neuroinflammation in a Mouse Model of Sarin Exposure. (Masters Thesis). Wright State University. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=wright1189715827

Chicago Manual of Style (16^th Edition):

Davidson, Molly Elizabeth. “Neurodegeneration and Neuroinflammation in a Mouse Model of Sarin Exposure.” 2007. Masters Thesis, Wright State University. Accessed July 22, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=wright1189715827.

MLA Handbook (7^th Edition):

Davidson, Molly Elizabeth. “Neurodegeneration and Neuroinflammation in a Mouse Model of Sarin Exposure.” 2007. Web. 22 Jul 2019.

Vancouver:

Davidson ME. Neurodegeneration and Neuroinflammation in a Mouse Model of Sarin Exposure. [Internet] [Masters thesis]. Wright State University; 2007. [cited 2019 Jul 22]. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=wright1189715827.

Council of Science Editors:

Davidson ME. Neurodegeneration and Neuroinflammation in a Mouse Model of Sarin Exposure. [Masters Thesis]. Wright State University; 2007. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=wright1189715827

University of Alberta

24. Mercer, Robert Corrigan Curtis. The Prion Protein: Modulation of Potassium Channels and a Novel Mouse Model of a Disease-Causing Hydrophobic Domain Insertion Mutation.

Degree: PhD, Department of Medicine, 2016, University of Alberta

URL: https://era.library.ualberta.ca/files/cmp48sc82v

► Prion diseases are invariably fatal neurodegenerative diseases of humans and other mammals. While they can manifest as sporadic, infectious or genetic etiologies, the central event… (more)

Subjects/Keywords: Gerstmann-Sträussler-Schienker; Potassium Channel; Prion; Neurodegeneration

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APA (6^th Edition):

Mercer, R. C. C. (2016). The Prion Protein: Modulation of Potassium Channels and a Novel Mouse Model of a Disease-Causing Hydrophobic Domain Insertion Mutation. (Doctoral Dissertation). University of Alberta. Retrieved from https://era.library.ualberta.ca/files/cmp48sc82v

Chicago Manual of Style (16^th Edition):

Mercer, Robert Corrigan Curtis. “The Prion Protein: Modulation of Potassium Channels and a Novel Mouse Model of a Disease-Causing Hydrophobic Domain Insertion Mutation.” 2016. Doctoral Dissertation, University of Alberta. Accessed July 22, 2019. https://era.library.ualberta.ca/files/cmp48sc82v.

MLA Handbook (7^th Edition):

Mercer, Robert Corrigan Curtis. “The Prion Protein: Modulation of Potassium Channels and a Novel Mouse Model of a Disease-Causing Hydrophobic Domain Insertion Mutation.” 2016. Web. 22 Jul 2019.

Vancouver:

Mercer RCC. The Prion Protein: Modulation of Potassium Channels and a Novel Mouse Model of a Disease-Causing Hydrophobic Domain Insertion Mutation. [Internet] [Doctoral dissertation]. University of Alberta; 2016. [cited 2019 Jul 22]. Available from: https://era.library.ualberta.ca/files/cmp48sc82v.

Council of Science Editors:

Mercer RCC. The Prion Protein: Modulation of Potassium Channels and a Novel Mouse Model of a Disease-Causing Hydrophobic Domain Insertion Mutation. [Doctoral Dissertation]. University of Alberta; 2016. Available from: https://era.library.ualberta.ca/files/cmp48sc82v

25. O HARA, DARREN. A Study of Mitochondrial Dynamics and Glycosylation Events in PC12 Cells and Neurons.

Degree: School of Biochemistry & Immunology. Discipline of Biochemistry, 2017, Trinity College Dublin

URL: http://hdl.handle.net/2262/81959

► Summary Mitochondrial dysfunction is recognised as a hallmark of many neurodegenerative diseases. Altered electron transport chain (ETC) complex activities, mitochondrial fusion/fission dynamics, mitochondrial motility kinetics… (more)

▼ Summary Mitochondrial dysfunction is recognised as a hallmark of many neurodegenerative diseases. Altered electron transport chain (ETC) complex activities, mitochondrial fusion/fission dynamics, mitochondrial motility kinetics and quality control of mitochondrial biogenesis have been implicated in the pathogenesis of Parkinson?s Disease (PD) and Alzheimer?s Disease (AD). However, further elucidation of the mechanisms that underlie dysfunctions in mitochondrial dynamics is required. This study characterizes the effect of electron transport chain (ETC) inhibition on mitochondrial dynamics in differentiated PC12 cells and primary cortical neurons. Inhibition of any of the ETC complexes, ATP synthase or dissipation of the mitochondrial membrane potential was sufficient to completely abolish mitochondrial fusion in differentiated PC12 cells. This effect is dependent on a post-translational modification that cleaves OPA1, the protein responsible for inner mitochondrial membrane fusion, to a shorter form, thus inhibiting fusion. It was also found that complex I inhibition has a threshold effect on mitochondrial fusion in primary cortical neurons as 55% inhibition of complex I completely inhibits mitochondrial fusion while 53% inhibition has no significant effect. This effect also correlated with a mitochondrial membrane potential dependent cleavage of Opa1. Mutations in, and abnormal accumulation of, the presynaptic protein a-synuclein are highly correlated with the pathogenesis of PD. Accumulations of this protein have been shown to inhibit complex I. Overexpression of both wild-type and mutant forms of a-synculein were found to decrease mitochondrial fusion in differentiated PC12 cells, suggesting that a-synculein dependent changes in fusion/fission dynamics may be a complicating factor in PD. Altered substrate utilization and O-GlcNAcylation have also been linked to the progression of some neurodegenerative diseases. In this study, inhibition of fatty acid oxidation and pyruvate transport into the mitochondrion decreased mitochondrial fusion in differentiated PC12 cells. O-GlcNAcylation is a post- translational modification that attaches O-GlcNAc moieties to cytoplasmic, nuclear and mitochondrial proteins. Investigation into acute increases in O- GlcNAcylation, induced by inhibition or knockdown of O-GlcNAcase, revealed decreases in mitochondrial fusion, elongated mitochondrial morphology, increased respiration rates and increased complex I activity. A decrease in the level of O-GlcNAcylation, induced by inhibition or knockdown of O-GlcNAc transferase, resulted in increased mitochondrial fusion, decreased mitochondrial membrane potential, fragmented mitochondrial morphology and decreased respiration rates in differentiated PC12 cells. Knockdown of O-GlcNAc transferase also resulted in increased ROS production. The results presented in this thesis point to altered complex I activity having an important role in mitochondrial dysfunction and subsequently, mitochondrial dynamics in the brain. Identification of compounds… Advisors/Committee Members: Davey, Gavin.

Subjects/Keywords: Mitochondria; Mitochondrial Dynamics; Neurodegeneration; Glycosylation; O-GlcNAc

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APA (6^th Edition):

O HARA, D. (2017). A Study of Mitochondrial Dynamics and Glycosylation Events in PC12 Cells and Neurons. (Thesis). Trinity College Dublin. Retrieved from http://hdl.handle.net/2262/81959

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):

O HARA, DARREN. “A Study of Mitochondrial Dynamics and Glycosylation Events in PC12 Cells and Neurons.” 2017. Thesis, Trinity College Dublin. Accessed July 22, 2019. http://hdl.handle.net/2262/81959.

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

MLA Handbook (7^th Edition):

O HARA, DARREN. “A Study of Mitochondrial Dynamics and Glycosylation Events in PC12 Cells and Neurons.” 2017. Web. 22 Jul 2019.

Vancouver:

O HARA D. A Study of Mitochondrial Dynamics and Glycosylation Events in PC12 Cells and Neurons. [Internet] [Thesis]. Trinity College Dublin; 2017. [cited 2019 Jul 22]. Available from: http://hdl.handle.net/2262/81959.

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

Council of Science Editors:

O HARA D. A Study of Mitochondrial Dynamics and Glycosylation Events in PC12 Cells and Neurons. [Thesis]. Trinity College Dublin; 2017. Available from: http://hdl.handle.net/2262/81959

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

26. Sundal, Christina. Hereditary diffuse leukoencephalopathy with spheroids: Insights into an adult onset neurodegenerative disease.

Degree: 2013, University of Gothenburg / Göteborgs Universitet

URL: http://hdl.handle.net/2077/31995

► During the last three decades, the areas of inherited white matter (WM) disorders have expanded. Advances in magnetic resonance imaging (MRI) and genetics have led… (more)

▼ During the last three decades, the areas of inherited white matter (WM) disorders have expanded. Advances in magnetic resonance imaging (MRI) and genetics have led to increased detection of adult-onset WM disorders. Hereditary diffuse leukoencephalopathy with spheroids (HDLS) is an adult-onset, invariably lethal, brain WM disorder with an autosomal dominant inheritance pattern. The clinical symptoms are characterized by a constellation of features that progress to a devastating disease with multiple neurological impairments. The neuropathological hallmarks of HDLS are demyelination and the presence of axonal spheroids. The overall aim of this study was to gather enough clinical cases, radiological images, cerebrospinal fluid (CSF) biomarkers and molecular genetic data to place HDLS in a nosographic context and define its relationship with other neurodegenerative disorders. We updated the original Swedish HDLS family and created a pedigree consisting of 166 individuals. Fifteen of those cases were affected with HDLS, including two new cases. The clinical course was different in the two recent cases, with a sub-acute and a more chronic variant, respectively. Familial clustering of HDLS is not always obvious and in the Mayo Clinic HDLS collection we found that all of our cases had been misdiagnosed with other more common neurological disorders. Using exome sequencing, we identified the colony stimulating factor 1 receptor (CSF1R) mutation in 14 Mayo Clinic HDLS families. MRIs of 15 of these CSF1R mutation carriers demonstrated asymmetric WM lesions (WML) with frontoparietal predominance. With diffusion weighted-, and diffusion tensor imaging (DTI/DWI) we defined three different stages of HDLS pathology, and detected a peripheral rim of restricted diffusion that had a centrifugal migration from the anterior ventricular horns. This might be pathognomonic for the original Swedish type of HDLS. In conclusion, HDLS is a distinct disease entity and the combination of clinical features such as frontal lobe syndromes, pyramidal-, extrapyramidal-, parietal- and visual signs, as well as WML in a characteristic frontoparietal distribution gives diagnostic clues. To clarify the distinction between the unknown genetics of the original Swedish family and the CSF1R mutation carriers, we propose to use molecular classification of HDLS type 1 and type 2, respectively. Results from our studies indicate that HDLS is probably primarily a neuroaxonal degeneration. Thus, elucidating the molecular mechanism of HDLS may provide novel insights into neurodegeneration.

Subjects/Keywords: HDLS; Neurodegeneration

…novel insights into neurodegeneration. 9 "Syftet med studien var att öka kunskapen om… …reasons it is now called pantothenate kinase-associated neurodegeneration (PKAN)… …the term “syndromes of neurodegeneration with brain iron accumulation,” (NBIA)…

10 more images…

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APA (6^th Edition):

Sundal, C. (2013). Hereditary diffuse leukoencephalopathy with spheroids: Insights into an adult onset neurodegenerative disease. (Thesis). University of Gothenburg / Göteborgs Universitet. Retrieved from http://hdl.handle.net/2077/31995

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):

Sundal, Christina. “Hereditary diffuse leukoencephalopathy with spheroids: Insights into an adult onset neurodegenerative disease.” 2013. Thesis, University of Gothenburg / Göteborgs Universitet. Accessed July 22, 2019. http://hdl.handle.net/2077/31995.

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

MLA Handbook (7^th Edition):

Sundal, Christina. “Hereditary diffuse leukoencephalopathy with spheroids: Insights into an adult onset neurodegenerative disease.” 2013. Web. 22 Jul 2019.

Vancouver:

Sundal C. Hereditary diffuse leukoencephalopathy with spheroids: Insights into an adult onset neurodegenerative disease. [Internet] [Thesis]. University of Gothenburg / Göteborgs Universitet; 2013. [cited 2019 Jul 22]. Available from: http://hdl.handle.net/2077/31995.

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

Council of Science Editors:

Sundal C. Hereditary diffuse leukoencephalopathy with spheroids: Insights into an adult onset neurodegenerative disease. [Thesis]. University of Gothenburg / Göteborgs Universitet; 2013. Available from: http://hdl.handle.net/2077/31995

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

Kent State University

27. Renszel, Krystal Marie. USING MUTAGENESIS AND STEM CELLS TO UNDERSTAND RETROVIRAL NEUROVIRULENCE.

Degree: MS, College of Arts and Sciences / School of Biomedical Sciences, 2009, Kent State University

URL: http://rave.ohiolink.edu/etdc/view?acc_num=kent1254659655

► Certain retroviruses are capable of causing progressive spongiform neurodegeneration which results in paralysis, wasting and death; however, the disease mechanism remains unknown. In this study,… (more)

Subjects/Keywords: Biomedical Research; retrovirus; neurodegeneration; protein glycosylation

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APA (6^th Edition):

Renszel, K. M. (2009). USING MUTAGENESIS AND STEM CELLS TO UNDERSTAND RETROVIRAL NEUROVIRULENCE. (Masters Thesis). Kent State University. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=kent1254659655

Chicago Manual of Style (16^th Edition):

Renszel, Krystal Marie. “USING MUTAGENESIS AND STEM CELLS TO UNDERSTAND RETROVIRAL NEUROVIRULENCE.” 2009. Masters Thesis, Kent State University. Accessed July 22, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=kent1254659655.

MLA Handbook (7^th Edition):

Renszel, Krystal Marie. “USING MUTAGENESIS AND STEM CELLS TO UNDERSTAND RETROVIRAL NEUROVIRULENCE.” 2009. Web. 22 Jul 2019.

Vancouver:

Renszel KM. USING MUTAGENESIS AND STEM CELLS TO UNDERSTAND RETROVIRAL NEUROVIRULENCE. [Internet] [Masters thesis]. Kent State University; 2009. [cited 2019 Jul 22]. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=kent1254659655.

Council of Science Editors:

Renszel KM. USING MUTAGENESIS AND STEM CELLS TO UNDERSTAND RETROVIRAL NEUROVIRULENCE. [Masters Thesis]. Kent State University; 2009. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=kent1254659655

Penn State University

28. Robinson, William Foster. Histologic and Electroretinographic Evidence of Diabetes-induced Retinal Neurodegeneration.

Degree: PhD, Anatomy, 2010, Penn State University

URL: https://etda.libraries.psu.edu/catalog/11412

► Diabetic retinopathy is a vision-threatening condition, currently affecting more than 5 million Americans. It is the leading cause of new cases of blindness in working-aged… (more)

▼ Diabetic retinopathy is a vision-threatening condition, currently affecting more than 5 million Americans. It is the leading cause of new cases of blindness in working-aged adults. The pathogenesis of the disease is poorly understood, but the earliest symptoms include subtle visual disturbances such as color and contrast sensitivity changes, delayed dark adaptation, and difficulty seeing in low-light environments. The earliest clinical signs of diabetic retinopathy are vascular abnormalities such as microaneurysms and edema. There is considerable evidence suggesting that retinal neurodegeneration takes place before the onset of such vascular changes. Previous research in our lab has established that retinal neurodegeneration is an apoptotic event, leading to retinal thinning. Animal models of experimental diabetes have been used to determine that retinal thinning takes place preferentially in the inner retina. The retinal ganglion cells are especially vulnerable, demonstrating the greatest loss in peripheral regions of the retina. The current study seeks to further explore the effects of diabetes on the neuronal components of retinas from human donors and from diabetic mice. The studies compiled here seek to test the hypotheses that early stages of diabetes lead to histologic evidence of neurodegeneration in human donor tissue, and that diabetes in the Ins2Akita mouse leads to alterations in rhodopsin content and electroretinographic output. Donor retinas from humans who had had diabetes for less than 10 years were compared with retinas from age-matched nondiabetic donors. Comparisons were made on the basis of retinal thickness and cell counts. Ins2Akita mice, which spontaneously develop diabetes at 4 weeks of age, were tested after being diabetic for 7 weeks. Electroretinograms were recorded and the following waveforms were analyzed for amplitude and implicit time: scotopic threshold response, a- and b- waves, and oscillatory potentials. Results of the human histopathology study indicate that, while there are no differences between retinal thickness measurements from diabetic vs. nondiabetic donors, the retinas from donors with short-term diabetes had fewer cells in the peripheral regions of the outer nuclear layer. Cell counts from the cone photoreceptors were unchanged, indicating rod loss. Studies of rod photoreceptor protein content demonstrated a decrease in rhodopsin content in diabetic mice, without a change in the protein content of other phototransduction proteins (transducin and phosphodiesterase). ERG results from diabetic mice demonstrate reduced scotopic threshold response and delayed oscillatory potentials, compared to age-matched controls. The findings presented here confirm that neurodegeneration takes place in the peripheral retina early in the progression of diabetes in humans. In contrast to animal models in which the inner retina is implicated, it may be that the photoreceptors of the outer retina are the cells most vulnerable to neurodegeneration in humans with diabetes. Diabetic mice, however,…

Subjects/Keywords: diabetes; retinopathy; neurodegeneration; photoreceptor; electroretinography; ERG; immunohistochemistry

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

APA (6^th Edition):

Robinson, W. F. (2010). Histologic and Electroretinographic Evidence of Diabetes-induced Retinal Neurodegeneration. (Doctoral Dissertation). Penn State University. Retrieved from https://etda.libraries.psu.edu/catalog/11412

Chicago Manual of Style (16^th Edition):

Robinson, William Foster. “Histologic and Electroretinographic Evidence of Diabetes-induced Retinal Neurodegeneration.” 2010. Doctoral Dissertation, Penn State University. Accessed July 22, 2019. https://etda.libraries.psu.edu/catalog/11412.

MLA Handbook (7^th Edition):

Robinson, William Foster. “Histologic and Electroretinographic Evidence of Diabetes-induced Retinal Neurodegeneration.” 2010. Web. 22 Jul 2019.

Vancouver:

Robinson WF. Histologic and Electroretinographic Evidence of Diabetes-induced Retinal Neurodegeneration. [Internet] [Doctoral dissertation]. Penn State University; 2010. [cited 2019 Jul 22]. Available from: https://etda.libraries.psu.edu/catalog/11412.

Council of Science Editors:

Robinson WF. Histologic and Electroretinographic Evidence of Diabetes-induced Retinal Neurodegeneration. [Doctoral Dissertation]. Penn State University; 2010. Available from: https://etda.libraries.psu.edu/catalog/11412

Penn State University

29. Hall II, Eric Christopher. The contribution of an iron genetic modifier, HFE, to Alzheimer's disease.

Degree: PhD, Neuroscience, 2009, Penn State University

URL: https://etda.libraries.psu.edu/catalog/10189

► Alzheimer’s disease (AD) is a neurodegenerative disorder of the human central nervous system characterized by loss of memory that leads to dementia. The pathological characteristics… (more)

▼ Alzheimer’s disease (AD) is a neurodegenerative disorder of the human central nervous system characterized by loss of memory that leads to dementia. The pathological characteristics of AD include an accumulation of amyloid-â (Aâ) plaques and aggregated hyperphosphorylated tau protein, neurofibrillary tangles (NFT), throughout the brain. Multiple hypotheses have been proposed to explain AD etiology including the loss of brain iron regulation. Among the areas investigated are the of variant forms of the HFE gene as a risk factor or disease modifier. HFE is an iron regulatory protein that limits cellular iron uptake. A mutation in the HFE gene can result in a loss of function. Epidemiological studies have investigated an association between HFE polymorphisms and AD risk; however these studies are not all in agreement. In order to determine more clearly how HFE could impact neurodegenerative processes, experiments in this thesis were designed to investigate the cellular contribution of the HFE H63D polymorphism in proposed AD pathogenic pathways. We utilized a novel stably transfected human neuroblastoma SH-SY5Y cell model expressing HFE polymorphisms for our studies. The thesis focused on three main areas: 1) HFE and amyloid regulation, 2) HFE and tau phosphorylation and 3) HFE effects on potential drug treatment strategies in AD. To evaluate amyloid regulation, we determined amyloid precursor protein (APP) synthesis, processing, and cellular vulnerability to Aâ toxicity in the presence of different forms of HFE. APP levels increased with HFE expression, although no effect of HFE variants was observed. There was no change in APP processing as determined by performing spectrofluorometric secretase-specific activity assays. We discovered that cells expressing the H63D variant are more sensitive to Aâ peptide exposure determined by MTT assay [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide]. There was an up-regulation of the intrinsic apoptotic pathway as determined by increases in caspase-9 expression, caspase-3 activity, and early apoptosis based on detection of Annexin V. It appeared that these changes were a result of mitochondria dysfunction in the cells expressing H63D because we also observed an increase in Bax in the cellular mitochondrial fraction and cytochrome C levels were increased in the cytosolic fraction. Mitochondria dysfunction and oxidative stress can act as indirect mechanisms to impact tau phosphorylation. Tau phosphorylation is regulated by a homeostasis of tau kinase and phosphatase activity that can be impacted by cellular stressors. In cells expressing the H63D polymorphism, tau phosphorylation was increased at serine-residues implicated in NFT generation. There was no change in phosphatase expression in H63D cells; yet there was an increase in glycogen synthase kinase-3 beta (GSK-3â) activity as determined by measuring GSK-3â phosphorylation at its serine-9 residue. The genotype associated alterations in GSK-3â activity with HFE expression prompted us to investigate the role of a…

Subjects/Keywords: amyloid; neurodegeneration; HFE; iron; tau; pin1

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

APA (6^th Edition):

Hall II, E. C. (2009). The contribution of an iron genetic modifier, HFE, to Alzheimer's disease. (Doctoral Dissertation). Penn State University. Retrieved from https://etda.libraries.psu.edu/catalog/10189

Chicago Manual of Style (16^th Edition):

Hall II, Eric Christopher. “The contribution of an iron genetic modifier, HFE, to Alzheimer's disease.” 2009. Doctoral Dissertation, Penn State University. Accessed July 22, 2019. https://etda.libraries.psu.edu/catalog/10189.

MLA Handbook (7^th Edition):

Hall II, Eric Christopher. “The contribution of an iron genetic modifier, HFE, to Alzheimer's disease.” 2009. Web. 22 Jul 2019.

Vancouver:

Hall II EC. The contribution of an iron genetic modifier, HFE, to Alzheimer's disease. [Internet] [Doctoral dissertation]. Penn State University; 2009. [cited 2019 Jul 22]. Available from: https://etda.libraries.psu.edu/catalog/10189.

Council of Science Editors:

Hall II EC. The contribution of an iron genetic modifier, HFE, to Alzheimer's disease. [Doctoral Dissertation]. Penn State University; 2009. Available from: https://etda.libraries.psu.edu/catalog/10189

Kent State University

30. Vignos, Megan C. A HISTOPATHOLOGICAL AND MAGNETIC RESONANCE IMAGING ASSESSMENT OF MYELOCORTICAL MULTIPLE SCLEROSIS: A NEW PATHOLOGICAL VARIANT.

Degree: PhD, College of Arts and Sciences / School of Biomedical Sciences, 2016, Kent State University

URL: http://rave.ohiolink.edu/etdc/view?acc_num=kent1461528682

► Multiple sclerosis (MS) is an inflammatory-mediated demyelinating, neurodegenerative disease characterized by a diverse clinical course and varying patterns of disease progression. It affects millions of… (more)

Subjects/Keywords: Biomedical Research; Multiple Sclerosis, Histopathology, MRI, Neurodegeneration

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

APA (6^th Edition):

Vignos, M. C. (2016). A HISTOPATHOLOGICAL AND MAGNETIC RESONANCE IMAGING ASSESSMENT OF MYELOCORTICAL MULTIPLE SCLEROSIS: A NEW PATHOLOGICAL VARIANT. (Doctoral Dissertation). Kent State University. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=kent1461528682

Chicago Manual of Style (16^th Edition):

Vignos, Megan C. “A HISTOPATHOLOGICAL AND MAGNETIC RESONANCE IMAGING ASSESSMENT OF MYELOCORTICAL MULTIPLE SCLEROSIS: A NEW PATHOLOGICAL VARIANT.” 2016. Doctoral Dissertation, Kent State University. Accessed July 22, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=kent1461528682.

MLA Handbook (7^th Edition):

Vignos, Megan C. “A HISTOPATHOLOGICAL AND MAGNETIC RESONANCE IMAGING ASSESSMENT OF MYELOCORTICAL MULTIPLE SCLEROSIS: A NEW PATHOLOGICAL VARIANT.” 2016. Web. 22 Jul 2019.

Vancouver:

Vignos MC. A HISTOPATHOLOGICAL AND MAGNETIC RESONANCE IMAGING ASSESSMENT OF MYELOCORTICAL MULTIPLE SCLEROSIS: A NEW PATHOLOGICAL VARIANT. [Internet] [Doctoral dissertation]. Kent State University; 2016. [cited 2019 Jul 22]. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=kent1461528682.

Council of Science Editors:

Vignos MC. A HISTOPATHOLOGICAL AND MAGNETIC RESONANCE IMAGING ASSESSMENT OF MYELOCORTICAL MULTIPLE SCLEROSIS: A NEW PATHOLOGICAL VARIANT. [Doctoral Dissertation]. Kent State University; 2016. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=kent1461528682

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