subject:(alpha7)

1. Doe, Jinger A. Enhanced alpha7beta1 integrin prevents muscle disease in a mouse model of congenital muscular dystrophy.

Degree: 2011, University of Nevada – Reno

URL: http://hdl.handle.net/11714/3913

► Merosin Deficient Congenital Muscular Dystrophy Type 1A (MDC1A) is the most common form of Congenital Muscular Dystrophy (CMD). MDC1A accounts for approximately 40% of all… (more)

▼ Merosin Deficient Congenital Muscular Dystrophy Type 1A (MDC1A) is the most common form of Congenital Muscular Dystrophy (CMD). MDC1A accounts for approximately 40% of all CMD cases. CMD is estimated to have an incidence rate in the United States of 1/100,000 live births. MDC1A is a lethal disease which results from mutations in the LAMA2 gene leading to either a complete or partial absence of the protein laminin α2. The loss of laminin α2 protein in turn leads to a failure to produce laminin 211 and laminin 221. Laminin 211 is the major laminin component of the basal lamina of mature skeletal muscle while laminin 221 is primarily located at neuromuscular and myotendinous junctions. Patients with MDC1A display a spectrum of clinical signs which correlate with the type of mutation they carry in the LAMA2 gene. Patients who produce some laminin α2 or who produce a truncated form of the protein tend to have less severe clinical signs and longer life expectancies than patients who produce no laminin α2. Patients with classic MDC1A have mutations which result in either complete absence of or negligible production of laminin α2. Patients who produce no laminin α2 have the most severe clinical signs and shortest life expectancies. MDC1A patients display delayed motor milestones and unsupported sitting is often the maximal motor activity; they are often confined to a wheelchair at a young age. Feeding problems requiring feeding tube placement, and respiratory difficulties requiring positive pressure ventilation are common. It is not unusual for these patients to die within the first decade of life due to respiratory complications.Secondary to the loss of laminin α2, MDC1A patients display reduced levels of α7 integrin. The α7β1 integrin is one of the main laminin 211/221 receptors in skeletal muscle. The loss of α7 integrin is considered to be due to communication between the extracellular matrix and the cell surface receptors. Primary loss of the α7 integrin is rare and leads to a myopathy in affected individuals. The effect of the secondary loss of the α7 integrin in MDC1A patients has not been evaluated prior to this work. In order to determine the effect of α7 integrin loss, we enhanced α7 integrin expression in the skeletal muscle of the dyW-/- mouse model of MDC1A. The dyW-/- mouse is one of the most commonly used models of MDC1A and displays altered expression and localization of the α7 integrin with little integrin appropriately localized to the sarcolemma. We accomplished forced expression of α7 integrin by breeding the BX2-10i mouse and dyW-/- mouse over several generations to develop a mouse which lacked laminin α2 and overexpressed α7 integrin in the skeletal muscle. The BX2-10i mouse is a skeletal muscle specific overexpressor of α7BX2 integrin - one of the primary α7 integrin isoforms which binds with laminin in skeletal muscle. These animals contain a transgene which… Advisors/Committee Members: Burkin, Dean J. (advisor), Kidd, Thomas (committee member), Leblanc, Normand (committee member), Singer, Cherie (committee member), Valencik, Maria (committee member).

Subjects/Keywords: Alpha7 Integrin; CMD; Integrin; MDC1A

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

APA (6^th Edition):

Doe, J. A. (2011). Enhanced alpha7beta1 integrin prevents muscle disease in a mouse model of congenital muscular dystrophy. (Thesis). University of Nevada – Reno. Retrieved from http://hdl.handle.net/11714/3913

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):

Doe, Jinger A. “Enhanced alpha7beta1 integrin prevents muscle disease in a mouse model of congenital muscular dystrophy.” 2011. Thesis, University of Nevada – Reno. Accessed January 16, 2021. http://hdl.handle.net/11714/3913.

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

MLA Handbook (7^th Edition):

Doe, Jinger A. “Enhanced alpha7beta1 integrin prevents muscle disease in a mouse model of congenital muscular dystrophy.” 2011. Web. 16 Jan 2021.

Vancouver:

Doe JA. Enhanced alpha7beta1 integrin prevents muscle disease in a mouse model of congenital muscular dystrophy. [Internet] [Thesis]. University of Nevada – Reno; 2011. [cited 2021 Jan 16]. Available from: http://hdl.handle.net/11714/3913.

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

Council of Science Editors:

Doe JA. Enhanced alpha7beta1 integrin prevents muscle disease in a mouse model of congenital muscular dystrophy. [Thesis]. University of Nevada – Reno; 2011. Available from: http://hdl.handle.net/11714/3913

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

Northeastern University

2. Kulkarni, Abhijit Raghunath. Novel allosteric modulators of α7 nicotinic acetylcholine receptor and development of efficient methodologies enabling synthesis of tetrahydroquinolines and unsymmetrical ureas.

Degree: PhD, School of Pharmacy, 2016, Northeastern University

URL: http://hdl.handle.net/2047/D20237784

► This thesis work encompasses the design, synthesis, and profiling of novel ligands (modulators) binding to an important molecular target, α7 nicotinic acetylcholine receptor (nAChR), which… (more)

▼ This thesis work encompasses the design, synthesis, and profiling of novel ligands (modulators) binding to an important molecular target, α7 nicotinic acetylcholine receptor (nAChR), which belongs to the ligand gated ion channel group of transmembrane ion channel proteins. Cellular signaling mediated by the α7 receptor is involved in homeostasis of various physiological systems and therefore is considered a crucial target for drug discovery. This work also includes development of novel methodologies in accelerating lead optimization through iterative/parallel synthesis of biologically relevant tetrahydroquinoline and unsymmetrical urea scaffolds using modern technologies such as the microwave synthesizer to significantly enhance the efficiency of the reaction by with improved yield and reduced reaction time.; The α7 nicotinic acetylcholine receptor (nAChR): The α7 nAChR is a homopentameric membrane protein located in the brain and the periphery, and gates the flux of several ions: Na+, K+ and Ca2+. It is a validated target for improving cognitive impairment associated with disease states such as Alzheimer's disease (AD) and schizophrenia and for treating pain and inflammation. In recent years, a variety of structurally distinct, subtype-selective and potent α7 nAChR agonists have been developed and profiled. However, there have been concerns regarding their clinical utility due to the idiosyncrasies of the receptor. An alternative mode of α7 nAChR signaling with positive allosteric modulators (PAMs) has shown significant potential in overcoming the limitations of orthosteric α7 nAChR agonists. PAMs can enhance the signaling efficacy of orthosteric α7 nAChR ligands with prolonged activity along with reduced risk of premature receptor desensitization.; Recently, compounds that, along with enhancing the effect of orthosteric ligands, can activate the α7 receptor from the allosteric site have been discovered (ago-PAMs). A relatively slow-desensitizing ago-PAM might be particularly beneficial compared to ligands with only PAM activity under severe loss of endogenous ACh such as in advanced AD. The overall goal of this project is to understand the structure-activity relationship (SAR) around a prototype ago-PAM, 4BP-TQS, develop more drug-like compounds with improved potency, efficacy and physicochemical properties and elucidate the allosteric binding site(s) in greater detail. My work has identified the stereochemical requirement for activity at α7 with GAT107 as the active (+) enantiomer of 4BP-TQS along with the synthesis and profiling of ~120 4BP-TQS analogs using our in-house microwave-assisted methodology to identify novel, efficacious ago-PAMs of the α7 receptor for multiple therapeutic utilities.; Enabling Technology for Rapid Synthesis of Cyclopentene-fused-Tetrahydroquinoline Scaffold: The synthesis of 4BP-TQS and related analogs with a cyclopentene ring fused to it, as reported in literature, has been time inefficient (>24 h) and relatively low yielding presumably due to thermal instability of cyclopentadiene…

Subjects/Keywords: allosteric; alpha7; cannabinoid; methodology; modulators; nicotinic

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APA (6^th Edition):

Kulkarni, A. R. (2016). Novel allosteric modulators of α7 nicotinic acetylcholine receptor and development of efficient methodologies enabling synthesis of tetrahydroquinolines and unsymmetrical ureas. (Doctoral Dissertation). Northeastern University. Retrieved from http://hdl.handle.net/2047/D20237784

Chicago Manual of Style (16^th Edition):

Kulkarni, Abhijit Raghunath. “Novel allosteric modulators of α7 nicotinic acetylcholine receptor and development of efficient methodologies enabling synthesis of tetrahydroquinolines and unsymmetrical ureas.” 2016. Doctoral Dissertation, Northeastern University. Accessed January 16, 2021. http://hdl.handle.net/2047/D20237784.

MLA Handbook (7^th Edition):

Kulkarni, Abhijit Raghunath. “Novel allosteric modulators of α7 nicotinic acetylcholine receptor and development of efficient methodologies enabling synthesis of tetrahydroquinolines and unsymmetrical ureas.” 2016. Web. 16 Jan 2021.

Vancouver:

Kulkarni AR. Novel allosteric modulators of α7 nicotinic acetylcholine receptor and development of efficient methodologies enabling synthesis of tetrahydroquinolines and unsymmetrical ureas. [Internet] [Doctoral dissertation]. Northeastern University; 2016. [cited 2021 Jan 16]. Available from: http://hdl.handle.net/2047/D20237784.

Council of Science Editors:

Kulkarni AR. Novel allosteric modulators of α7 nicotinic acetylcholine receptor and development of efficient methodologies enabling synthesis of tetrahydroquinolines and unsymmetrical ureas. [Doctoral Dissertation]. Northeastern University; 2016. Available from: http://hdl.handle.net/2047/D20237784

3. M. Quadri. INVESTIGATION OF THE ROLE OF ALPHA7 NICOTINIC ACETYLCHOLINE RECEPTORS IN INFLAMMATORY DISEASES THROUGH THE DESIGN, SYNTHESIS AND BIOLOGICAL EVALUATION OF NEW HETEROCYCLIC DERIVATIVES.

Degree: 2015, Università degli Studi di Milano

URL: http://hdl.handle.net/2434/345989

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La ricerca sviluppata con il presente progetto di Dottorato è rivolta all’approfondimento del ruolo del recettore nicotinico alfa7 nella cascata infiammatoria colinergica attraverso la progettazione,… (more)

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La ricerca sviluppata con il presente progetto di Dottorato è rivolta all’approfondimento del ruolo del recettore nicotinico alfa7 nella cascata infiammatoria colinergica attraverso la progettazione, la sintesi e la valutazione farmacologica di nuovi derivati eterociclici in grado di interagire e attivare selettivamente questo sottotipo recettoriale. A tale scopo, sono stati progettati nuovi modulatori allosterici positivi (PAMs) o agonisti silenti del recettore nicotinico alfa7. Per ottenere i nuovi PAMs, caratterizzati da migliore potenza e selettività, è stato applicato l’approccio di ibridizzazione molecolare ai due PAMs di tipo I, il 5-idrossindolo (5-HI) e la genisteina. Il nucleo eteroaromatico del 5-HI è stato connesso a un anello benzenico variamente funzionalizzato sfruttando due diversi posizioni di connessione, l’azoto indolico e il carbonio in posizione 2, e sono state pertanto ottenute due serie parallele di composti. Inoltre, l’attivazione del recettore alfa7 è stata studiata attraverso la preparazione di agonisti silenti, in grado di trasmettere il segnale recettoriale con un meccanismo indipendente dall’apertura del canale e dal passaggio della corrente ionica. Con l’intento di chiarire il modello farmacoforico di tali nuovi agonisti alfa7 e di approfondirne il profilo farmacologico, tre serie di derivati sono state progettate e sintetizzate. La prima comprende derivati strutturalmente correlati al diEPP, recentemente emerso come agonista silente del recettore alfa7. Le altre due serie di composti sono state progettate inserendo il nucleo azabiciclico chinuclidinico, legato in forma spirociclica all’anello Delta2-isossazolinico o connesso a un eterociclo 1,2,4-ossadiazolico, per valutare l’importanza del centro basico quale requisito fondamentale nel modello farmacoforico noto. Il profilo farmacologico dei nuovi derivati è stato studiato in saggi elettrofisiologici su oociti di Xenopus che esprimono il recettore umano alfa7. Nella serie dei derivati del 5-idrossindolo, tre composti hanno mostrato un’attività allosterica positiva migliore rispetto al composto di riferimento. L’indagine farmacologica sui potenziali agonisti silenti è tuttora in corso. Attualmente sono disponibili i dati preliminari solo per la serie dei diEPP derivati e quattro composti si sono rivelati caratterizzati da un agonismo silente fino a 46 volte maggiore rispetto al composto parente.

The current PhD research project aimed at investigating the role of the alpha7 nAChRs in the cholinergic inflammatory cascade through the design, synthesis and pharmacological evaluation of novel heterocyclic ligands targeting and selectively activating this receptor subtype. To this purpose, new sets of compounds acting as positive allosteric modulators (PAMs) or silent agonists were planned. In order to achieve new alpha7 PAMs endowed with enhanced allosteric activity and selectivity, the molecular hybridization approach was applied to the type I PAMs, 5-hydroxyindole (5-HI) and genistein. Therefore, the heteroaromatic nucleus of 5-HI was…

Advisors/Committee Members: tutor: C. Dallanoce, coordinatore: M. De Amici, DALLANOCE, CLELIA MARIANGIOLA LUISA, DE AMICI, MARCO.

Subjects/Keywords: alpha7 nicotinic receptors; alpha7 nicotinic ligands; positive allosteric modulation; silent agonism; inflammation; electrophysiological assays; Settore CHIM/08 - Chimica Farmaceutica

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

APA (6^th Edition):

Quadri, M. (2015). INVESTIGATION OF THE ROLE OF ALPHA7 NICOTINIC ACETYLCHOLINE RECEPTORS IN INFLAMMATORY DISEASES THROUGH THE DESIGN, SYNTHESIS AND BIOLOGICAL EVALUATION OF NEW HETEROCYCLIC DERIVATIVES. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/345989

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):

Quadri, M.. “INVESTIGATION OF THE ROLE OF ALPHA7 NICOTINIC ACETYLCHOLINE RECEPTORS IN INFLAMMATORY DISEASES THROUGH THE DESIGN, SYNTHESIS AND BIOLOGICAL EVALUATION OF NEW HETEROCYCLIC DERIVATIVES.” 2015. Thesis, Università degli Studi di Milano. Accessed January 16, 2021. http://hdl.handle.net/2434/345989.

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

MLA Handbook (7^th Edition):

Quadri, M.. “INVESTIGATION OF THE ROLE OF ALPHA7 NICOTINIC ACETYLCHOLINE RECEPTORS IN INFLAMMATORY DISEASES THROUGH THE DESIGN, SYNTHESIS AND BIOLOGICAL EVALUATION OF NEW HETEROCYCLIC DERIVATIVES.” 2015. Web. 16 Jan 2021.

Vancouver:

Quadri M. INVESTIGATION OF THE ROLE OF ALPHA7 NICOTINIC ACETYLCHOLINE RECEPTORS IN INFLAMMATORY DISEASES THROUGH THE DESIGN, SYNTHESIS AND BIOLOGICAL EVALUATION OF NEW HETEROCYCLIC DERIVATIVES. [Internet] [Thesis]. Università degli Studi di Milano; 2015. [cited 2021 Jan 16]. Available from: http://hdl.handle.net/2434/345989.

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

Council of Science Editors:

Quadri M. INVESTIGATION OF THE ROLE OF ALPHA7 NICOTINIC ACETYLCHOLINE RECEPTORS IN INFLAMMATORY DISEASES THROUGH THE DESIGN, SYNTHESIS AND BIOLOGICAL EVALUATION OF NEW HETEROCYCLIC DERIVATIVES. [Thesis]. Università degli Studi di Milano; 2015. Available from: http://hdl.handle.net/2434/345989

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

4. V. Alari. CARATTERIZZAZIONE MOLECOLARE E FUNZIONALE DEL GENE CHRFAM7A, FORMA DUPLICATA DELLA SUBUNITÀ ALPHA7 DEL RECETTORE NICOTINICO.

Degree: 2013, Università degli Studi di Milano

URL: http://hdl.handle.net/2434/215883

► The α7 nicotinic acetylcholine receptor (α7 nAChR) has a key role in the innate immune system’s inflammatory response, as part of “cholinergic anti-inflammatory pathway”: a… (more)

▼ The α7 nicotinic acetylcholine receptor (α7 nAChR) has a key role in the innate immune system’s inflammatory response, as part of “cholinergic anti-inflammatory pathway”: a process by which acetylcholine from the vagus nerve reduces the release of the pro-inflammatory cytokine TNFα, thus allowing for a controlled response to infection. The CHRNA7 gene, in humans, is partially duplicated from exon 5-10 and forms an hybrid with four exons (D-A) of a novel gene, FAM7A. This new gene, CHRFAM7A, which is located in the opposite orientation, at 1.6 Mb, from CHRNA7, is not present on every chromosome 15 and a polymorphic variant, in linkage disequilibrium with a 2bp deletion in exon 6, in the same orientation to the CHRNA7 gene, has been described in a cohort of patients with bipolar disorders and schizophrenia. THP-1 monocytic-like cell line expresses only CHRFAM7A, which was down-regulated on treatment with LPS, by a direct transcriptional mechanism reliant on NF-kB. This effect has been confirmed in primary monocytes and macrophages cell cultures, where CHRFAM7A is expressed 200-1000 times more than CHRNA7. Here, the conventional α7 subunit was up-regulated by LPS treatment, thus suggesting the involvement of CHRFAM7A in the regulation of cell surface α7 receptors’ level (a mechanism unique to humans) and the ability of immune cells to respond to acetylcholine, released from the vagus nerve, during infection. This hypothesis seems to be supported by recent works showing that the duplicated form may have a dominant negative effect on the activity of α7 nAChR. Infact, co-expression of CHRFAM7A with α7 results in a significant reduction of the Ach-evoked currents, suggesting the presence of heteromeric non functional receptors at the plasma membrane. The promoter region that regulates the expression of CHRFAM7A is still unknown. To try to identify and characterize this region, 5'-RACE experiments were carried out to map the CHRFAM7A mRNA 5’UTR. RNA was extracted from three different cell lines: THP-1 cells, primary human macrophages and SHSY5Y neuroblastoma cell line. Multiple transcription start sites were identified, depending on the cell line used, suggesting the existence of alternative promoters. A series of constructs that recapitulate the mapping of the CHRFAM7A regulatory region, according to the transcription start sites identified, was also generated. They were cloned into a reporter vector and their functionality was tested by transient transfection both in THP-1 and SHSY5Y cell models. Through these experiments, an intronic region (-702/-208 bp from ATG codon, in exon B) and an Alu sequence (-1155/-821 bp) were identified as negative regulators of reporter gene transcription. Future experiments will allow us to identify other regulatory sites, important for proper CHRFAM7A gene expression in different tissues. Furthermore, two variants exist for CHRFAM7A gene, due to alternative splicing, that gives rise to two protein products of predicted 36 and 47 KDa, whose function is currently unknown. The N-terminally… Advisors/Committee Members: tutor:D. Fornasari, coordinatore: A. Gianni, FORNASARI, DIEGO MARIA MICHELE, GIANNI, ALESSANDRO.

Subjects/Keywords: CHRFAM7A; cholinergic anti-inflammatory pathway; CHRNA7; alpha7; Settore BIO/14 - Farmacologia

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

APA (6^th Edition):

Alari, V. (2013). CARATTERIZZAZIONE MOLECOLARE E FUNZIONALE DEL GENE CHRFAM7A, FORMA DUPLICATA DELLA SUBUNITÀ ALPHA7 DEL RECETTORE NICOTINICO. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/215883

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):

Alari, V.. “CARATTERIZZAZIONE MOLECOLARE E FUNZIONALE DEL GENE CHRFAM7A, FORMA DUPLICATA DELLA SUBUNITÀ ALPHA7 DEL RECETTORE NICOTINICO.” 2013. Thesis, Università degli Studi di Milano. Accessed January 16, 2021. http://hdl.handle.net/2434/215883.

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

MLA Handbook (7^th Edition):

Alari, V.. “CARATTERIZZAZIONE MOLECOLARE E FUNZIONALE DEL GENE CHRFAM7A, FORMA DUPLICATA DELLA SUBUNITÀ ALPHA7 DEL RECETTORE NICOTINICO.” 2013. Web. 16 Jan 2021.

Vancouver:

Alari V. CARATTERIZZAZIONE MOLECOLARE E FUNZIONALE DEL GENE CHRFAM7A, FORMA DUPLICATA DELLA SUBUNITÀ ALPHA7 DEL RECETTORE NICOTINICO. [Internet] [Thesis]. Università degli Studi di Milano; 2013. [cited 2021 Jan 16]. Available from: http://hdl.handle.net/2434/215883.

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

Council of Science Editors:

Alari V. CARATTERIZZAZIONE MOLECOLARE E FUNZIONALE DEL GENE CHRFAM7A, FORMA DUPLICATA DELLA SUBUNITÀ ALPHA7 DEL RECETTORE NICOTINICO. [Thesis]. Università degli Studi di Milano; 2013. Available from: http://hdl.handle.net/2434/215883

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

Northeastern University

5. Garg, Brijesh. Investigating the role of α7 nicotinic receptors in inflammation.

Degree: PhD, School of Pharmacy, 2017, Northeastern University

URL: http://hdl.handle.net/2047/D20284519

► Alpha7 nicotinic acetylcholine receptors (α7 nAChRs) are ligand-gated ion-channels located in brain, retina, autonomic ganglia and some immune cells such as macrophages. α7 nAChRs have… (more)

▼ Alpha7 nicotinic acetylcholine receptors (α7 nAChRs) are ligand-gated ion-channels located in brain, retina, autonomic ganglia and some immune cells such as macrophages. α7 nAChRs have emerged as a novel target to inhibit peripheral inflammation by blocking the transcription factor, nuclear factor kappa-light chain-enhancer of B cells (NFΚB). α7 nAChR agonists including nicotine and GTS-21 have shown great promise in reducing levels of the pro-inflammatory cytokines such as interleukin-6 (IL6) and tumor-necrosis factor (TNF) in murine endotoxemia and severe sepsis models in vivo. However, mechanistic aspects of GTS-21effects on inflammatory pathways are largely unexplored. Here we used GH4C1 cells overexpressing α7 nAChR to evaluate the effects of nicotine and GTS-21 on TNF-induced NFΚB signaling. We also compared cell-type dependent responses of both α7 nAChR agonists in GH4C1 cells (non-immune cells), RAW264.7 cells (macrophage-like immune cells) and in ex vivo cultures of primary mouse macrophages. Nicotine and GTS-21 do not block TNF-stimulated NFΚB signaling in GH4C1 cells overexpressing α7 nAChRs, suggesting that they require additional unidentified factors, other than α7 nAChRs, for this anti-inflammatory effect. GTS-21 dose-dependently suppressed lipopolysaccharide (LPS)-induced TNF secretion in RAW264.7 cells lacking α7 nAChRs and primary mouse macrophages expressing them. In contrast, GTS-21 blocked IL6 secretion in primary mouse macrophages but had no effect in RAW264.7 cells. Similarly, nicotine inhibited LPS-activated IL6 and TNF secretion in primary mouse macrophages; however it had no effect on endotoxin-activated RAW264.7 cells. Moreover, α7 nAChR antagonism, using either methyllycaconitine (MLA) or α-bungarotoxin (αBGT), partially reversed nicotine or GTS-21 blockade of IL6 and TNF secretion in primary mouse macrophages. Since anti-inflammatory effects of nicotine were smaller than those of GTS-21 in mouse macrophages and because α7 nAChR involvement in nicotine's effects have been well characterized in macrophages, we used α7 nAChR-knockout (Chrna7-/-) mouse models to measure the importance of α7 nAChR in GTS-21 mediated anti-inflammatory effects. GTS-21 significantly inhibited LPS-induced IL6 and TNF production in Chrna7-/- mouse macrophages. These data indicate that even though a component of the GTS-21 anti-inflammatory effects requires an α7 nAChR presence, GTS-21 also has anti-inflammatory effects independent of α7 nAChR receptors, and these effects depend on the cell type.; Because α7 nAChRs are implicated in several disorders such as Alzheimer's, Parkinson's, schizophrenia, and inflammation and are involved in memory and cognition, validated methods to detect and localize these receptors are highly desirable. However, questions have been raised about the utility of commercially available α7 nAChR antibodies to detect rat α7 nAChRs. We therefore developed a gel-shift assay for western blots using GH4C1 cells overexpressing rat α7 nAChR and rat α7 nAChR-green fluorescent protein (GFP) construct…

Subjects/Keywords: alpha7 nicotinic acetylcholine receptors; anti-inflammatory effects; ulcerative colitis

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

APA (6^th Edition):

Garg, B. (2017). Investigating the role of α7 nicotinic receptors in inflammation. (Doctoral Dissertation). Northeastern University. Retrieved from http://hdl.handle.net/2047/D20284519

Chicago Manual of Style (16^th Edition):

Garg, Brijesh. “Investigating the role of α7 nicotinic receptors in inflammation.” 2017. Doctoral Dissertation, Northeastern University. Accessed January 16, 2021. http://hdl.handle.net/2047/D20284519.

MLA Handbook (7^th Edition):

Garg, Brijesh. “Investigating the role of α7 nicotinic receptors in inflammation.” 2017. Web. 16 Jan 2021.

Vancouver:

Garg B. Investigating the role of α7 nicotinic receptors in inflammation. [Internet] [Doctoral dissertation]. Northeastern University; 2017. [cited 2021 Jan 16]. Available from: http://hdl.handle.net/2047/D20284519.

Council of Science Editors:

Garg B. Investigating the role of α7 nicotinic receptors in inflammation. [Doctoral Dissertation]. Northeastern University; 2017. Available from: http://hdl.handle.net/2047/D20284519

6. Van Ry, Pam Marie. Protein Therapy for Muscular Dystrophy and Other Muscle Diseases.

Degree: 2014, University of Nevada – Reno

URL: http://hdl.handle.net/11714/2928

► Despite the exponential advancements in understanding the underlying cause of muscular diseases, there has been little progress in developing an effective treatment which results in… (more)

Subjects/Keywords: alpha7 beta1 integrin; Duchenne Muscular Dystrophy; MDC1A; Muscular Dystrophy; Protein; Therapy

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

APA (6^th Edition):

Van Ry, P. M. (2014). Protein Therapy for Muscular Dystrophy and Other Muscle Diseases. (Thesis). University of Nevada – Reno. Retrieved from http://hdl.handle.net/11714/2928

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):

Van Ry, Pam Marie. “Protein Therapy for Muscular Dystrophy and Other Muscle Diseases.” 2014. Thesis, University of Nevada – Reno. Accessed January 16, 2021. http://hdl.handle.net/11714/2928.

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

MLA Handbook (7^th Edition):

Van Ry, Pam Marie. “Protein Therapy for Muscular Dystrophy and Other Muscle Diseases.” 2014. Web. 16 Jan 2021.

Vancouver:

Van Ry PM. Protein Therapy for Muscular Dystrophy and Other Muscle Diseases. [Internet] [Thesis]. University of Nevada – Reno; 2014. [cited 2021 Jan 16]. Available from: http://hdl.handle.net/11714/2928.

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

Council of Science Editors:

Van Ry PM. Protein Therapy for Muscular Dystrophy and Other Muscle Diseases. [Thesis]. University of Nevada – Reno; 2014. Available from: http://hdl.handle.net/11714/2928

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

7. Pons, Mégane. Vers un traitement de la maladie d'Alzheimer : synthèse de nouveaux ligands multi-cibles : Toward an innovative treatment of Alzheimer's disease : Design of novel multi-target directed ligands.

Degree: Docteur es, Chimie, 2019, Normandie

URL: http://www.theses.fr/2019NORMR082

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La maladie d’Alzheimer (MA) est une maladie neurodégénérative complexe caractérisée par une perte progressive de la mémoire et de la cognition. C’est la première cause… (more)

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La maladie d’Alzheimer (MA) est une maladie neurodégénérative complexe caractérisée par une perte progressive de la mémoire et de la cognition. C’est la première cause de démence chez le sujet âgé et affecte environs 4.6 millions de personnes par an, selon un rapport de l’association « Alzheimer’s disease International », le nombre de patients pourrait s’élever à 135.5 millions en 2050. Du fait de sa complexité, la MA reste incurable et seuls 4 médicaments aux vertus palliatives dont 3 visant à inhiber l’acétylcholinestérase (AChE) ont reçu une autorisation de mise sur le marché à ce jour. L’approche multi-cible parait particulièrement adaptée du fait du grand nombre de cibles potentielles de la pathologie, et du caractère multifactoriel de la maladie. Cette approche consiste à associer sur une seule molécule, plusieurs pharmacophores afin qu’ils puissent agir simultanément sur différentes cibles impliquées dans le processus neurodégénératif. Dans ce contexte, en parallèle de la resynthèse d’un ligand multi-cible conjugué alliant un inhibiteur d’AChE (IAChE) et un antioxydant, deux nouvelles familles de ligands multi-cibles conjuguées, combinant un IAChE et un agoniste des récepteurs nicotiniques α7 (α7 nAChR) ont été conçues et leur synthèse abordée. Dans le cas de la première famille, le fragment ivastigmine a été choisi pour sa capacité à inhiber de manière pseudo-irréversible l’AChE et a été conjugué à un motif quinuclidine, un puissant agoniste des α7 nAChRs impliqués dans la MA. En combinant ces deux fragments, il a été observé que les propriétés biologiques in vitro de chaque pharmacophore étaient améliorées. La structure de la seconde famille est basée sur le Donepezil, un IAChE réversible de plus forte affinité, combiné au même motif quinuclidine que dans la série précédente. Si des intermédiaires avancés ont été obtenus, un ou deux étapes restent à finaliser pour finaliser la synthèse de cette troisième famille de MTDL.

Alzheimer’s disease (AD) is a complex neurodegenerative disease characterised by a progressive loss of memory and cognition. Nowadays, 4.6 million new patients are identified every year and according to the “Alzheimer’s diseases International” association, the number of patients could reach 135.5 million in 2050. Due to its complexity, AD remains uncurable and only 4 palliative drugs, of which 3 are acetylcholinesterase (AChE) inhibitors (AChEI), have been approved by FDA to date. AD being a multifactorial illness, with many potential targets involved in the pathology, the MTDL approach seems promising. This strategy associates in one single molecule, different pharmacophores (at least) acting on different targets involved in this CNS-related disorder. In this context, in parallel with the upscaled synthesis of a conjugated MTDL combining an AChEI inhibitor and an antioxidant, two new families of conjugated MTDLs associating an AChEI and a α7 nicotinic receptor (α7 nAChR) agonist have been investigated. The structure of the first family was based on a Rivastigmine scaffold, known to be a…

Advisors/Committee Members: Renard, Pierre-Yves (thesis director), Jean, Ludovic (thesis director).

Subjects/Keywords: Maladie d'Alzheimer; Ligand multi-cibles; Acétylcholinestérase; Antioxydant; Récepteur nicotinique alpha7; Huprine; Rivastigmine; Donepezil; Alzheimer's disease; Multi-target ligand; Acetylcholinesterase; Antioxidant; Alpha7 nicotinic receptor; Huprine; Rivastigmine; Donepezil; 615.58

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

APA (6^th Edition):

Pons, M. (2019). Vers un traitement de la maladie d'Alzheimer : synthèse de nouveaux ligands multi-cibles : Toward an innovative treatment of Alzheimer's disease : Design of novel multi-target directed ligands. (Doctoral Dissertation). Normandie. Retrieved from http://www.theses.fr/2019NORMR082

Chicago Manual of Style (16^th Edition):

Pons, Mégane. “Vers un traitement de la maladie d'Alzheimer : synthèse de nouveaux ligands multi-cibles : Toward an innovative treatment of Alzheimer's disease : Design of novel multi-target directed ligands.” 2019. Doctoral Dissertation, Normandie. Accessed January 16, 2021. http://www.theses.fr/2019NORMR082.

MLA Handbook (7^th Edition):

Pons, Mégane. “Vers un traitement de la maladie d'Alzheimer : synthèse de nouveaux ligands multi-cibles : Toward an innovative treatment of Alzheimer's disease : Design of novel multi-target directed ligands.” 2019. Web. 16 Jan 2021.

Vancouver:

Pons M. Vers un traitement de la maladie d'Alzheimer : synthèse de nouveaux ligands multi-cibles : Toward an innovative treatment of Alzheimer's disease : Design of novel multi-target directed ligands. [Internet] [Doctoral dissertation]. Normandie; 2019. [cited 2021 Jan 16]. Available from: http://www.theses.fr/2019NORMR082.

Council of Science Editors:

Pons M. Vers un traitement de la maladie d'Alzheimer : synthèse de nouveaux ligands multi-cibles : Toward an innovative treatment of Alzheimer's disease : Design of novel multi-target directed ligands. [Doctoral Dissertation]. Normandie; 2019. Available from: http://www.theses.fr/2019NORMR082

8. M.C. Pismataro. DESIGN AND SYNTHESIS OF NOVEL MOLECULAR PROBES TARGETING THE ALPHA7 NICOTINIC ACETYLCHOLINE RECEPTORS: INSIGHT INTO THE MECHANISMS OF ACTIVATION AND THE RELATED THERAPEUTIC IMPLICATIONS.

Degree: 2019, Università degli Studi di Milano

URL: http://hdl.handle.net/2434/615268

► Abstract - The α7 nicotinic acetylcholine receptor (nAChR) is a homopentameric ion channel, characterized by both ionotropic and metabotropic activation modes. The channel-dependent activation has… (more)

▼ Abstract - The α7 nicotinic acetylcholine receptor (nAChR) is a homopentameric ion channel, characterized by both ionotropic and metabotropic activation modes. The channel-dependent activation has been deeply investigated and its modulation was proven to be a promising therapeutic approach for diseases of the central nervous system (CNS) including Alzheimer’s disease, Parkinson’s disease, schizophrenia, autism, attention deficit hyperactivity disorder (ADHD), anxiety and depression. The additional metabotropic-like activity, instead, is now considered a key functional aspect of α7 nAChR signaling, especially in non-neuronal cells. In particular, in the immune cells, the α7 subtype plays a central role in anti-inflammatory processes via G-protein-mediated activation. The hypothesis defining a relationship between the non-ionotropic activity of α7 nAChRs and their desensitized states is an emerging research topic. The ability of a new class of compounds, defined as “silent agonists”, to stabilize the desensitized states of this receptor subtype engendering anti-inflammatory responses, most likely via a metabotropic mechanism, would seem to confirm this hypothesis. In this research project, the in-depth investigation of the alternative metabotropic-like modulation was performed through the study of structure-activity relationships of two well-known silent agonists, NS6740 and KC-1. The two model compounds were taken as reference structures owing to their relevant silent agonist behavior as well as the presence of common features in their molecular skeleton. Moreover, NS6740 showed a promising anti-inflammatory profile in both in vitro and in vivo assays. From the comparison of the structures of NS6740 (1,4-diazabicyclo[3.2.2]-non-4-yl[5-[3-(trifluoromethyl)phenyl]-2-furanyl]methanone) and KC-1 (5’-phenyl-anabaseine), a preliminary pharmacophore model had been proposed. Three main features were identified: a positively charged center, a central hydrogen-bond acceptor group and an aromatic moiety. In order to provide a deeper description of the pharmacophoric requirements and to achieve a better understanding of both steric and electronic features able to promote the silent agonist profile, several modifications were performed on the key pharmacophoric portions of NS6740 and KC-1. The NS6740 derivatives were synthesized through an acylation reaction between diverse diazabicyclic nuclei and differently substituted, previously prepared, aromatic chains. The New KC-1 derivatives were, instead, prepared via a Suzuki-Miyaura reaction between the central heteroaromatic ring and a set of differently substituted aromatic groups, followed by organolithium coupling with protected lactams. All the newly synthesized compounds were assayed employing human α7 nAChRs expressed in Xenopus laevis oocytes in two-electrode voltage clamping experiments. The results obtained from the electrophysiological investigations demonstrated that the three pharmacophoric moieties are essential to preserve the peculiar silent receptor activation… Advisors/Committee Members: supervisor: C. Dallanoce, coordinator: G. Aldini, DALLANOCE, CLELIA MARIANGIOLA LUISA, ALDINI, GIANCARLO, DALLANOCE, CLELIA MARIANGIOLA LUISA.

Subjects/Keywords: alpha7 nicotinic acetycholine receptor; silent agonist; inflammation; Settore CHIM/08 - Chimica Farmaceutica

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

APA (6^th Edition):

Pismataro, M. (2019). DESIGN AND SYNTHESIS OF NOVEL MOLECULAR PROBES TARGETING THE ALPHA7 NICOTINIC ACETYLCHOLINE RECEPTORS: INSIGHT INTO THE MECHANISMS OF ACTIVATION AND THE RELATED THERAPEUTIC IMPLICATIONS. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/615268

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):

Pismataro, M.C.. “DESIGN AND SYNTHESIS OF NOVEL MOLECULAR PROBES TARGETING THE ALPHA7 NICOTINIC ACETYLCHOLINE RECEPTORS: INSIGHT INTO THE MECHANISMS OF ACTIVATION AND THE RELATED THERAPEUTIC IMPLICATIONS.” 2019. Thesis, Università degli Studi di Milano. Accessed January 16, 2021. http://hdl.handle.net/2434/615268.

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

MLA Handbook (7^th Edition):

Pismataro, M.C.. “DESIGN AND SYNTHESIS OF NOVEL MOLECULAR PROBES TARGETING THE ALPHA7 NICOTINIC ACETYLCHOLINE RECEPTORS: INSIGHT INTO THE MECHANISMS OF ACTIVATION AND THE RELATED THERAPEUTIC IMPLICATIONS.” 2019. Web. 16 Jan 2021.

Vancouver:

Pismataro M. DESIGN AND SYNTHESIS OF NOVEL MOLECULAR PROBES TARGETING THE ALPHA7 NICOTINIC ACETYLCHOLINE RECEPTORS: INSIGHT INTO THE MECHANISMS OF ACTIVATION AND THE RELATED THERAPEUTIC IMPLICATIONS. [Internet] [Thesis]. Università degli Studi di Milano; 2019. [cited 2021 Jan 16]. Available from: http://hdl.handle.net/2434/615268.

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

Council of Science Editors:

Pismataro M. DESIGN AND SYNTHESIS OF NOVEL MOLECULAR PROBES TARGETING THE ALPHA7 NICOTINIC ACETYLCHOLINE RECEPTORS: INSIGHT INTO THE MECHANISMS OF ACTIVATION AND THE RELATED THERAPEUTIC IMPLICATIONS. [Thesis]. Università degli Studi di Milano; 2019. Available from: http://hdl.handle.net/2434/615268

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

University of South Florida

9. Schaal, Courtney. Regulation of nAChRs and Stemness by Nicotine and E-cigarettes in NSCLC.

Degree: 2016, University of South Florida

URL: https://scholarcommons.usf.edu/etd/6582

► Lung cancer is the leading cause of cancer-related death in both men and women, nationally and internationally and kills more people each year than breast,… (more)

▼ Lung cancer is the leading cause of cancer-related death in both men and women, nationally and internationally and kills more people each year than breast, prostate, and colon cancers combined. Non-small cell lung carcinoma (NSCLC) is the most common histological subtype of lung cancer, and accounts for 85% of all cases. Cigarette smoking is the single greatest risk factor for lung cancer, and is correlated with 80-90% of all lung cancer deaths. Nicotine, the addictive component of tobacco smoke, is not a carcinogen and cannot initiate tumors itself; however, it is known to act as a tumor promoter, by enhancing the proliferation, migration, and invasion of cells in vitro, thus accelerating tumor growth and metastasis in vivo. Nicotine exerts is tumor promoting effects primarily by binding to, and activation of, nicotinic acetylcholine receptors (nAChRs), specifically the α7 subunit of nAChRs. While α7 nAChR is expressed in a wide array of cells, how its expression is regulated is not fully understood. Here we sought to elucidate the transcriptional regulation of α7 nAChR in NSCLC cells. We report that α7 nAChR expression is induced by nicotine in an autoregulatory feedforward loop, and that the α7 gene promoter is differentially regulated by E2F1 and STAT1 transcription factors at an overlapping binding site suggesting a competitive interplay. Depletion of E2F1 resulted in a reduced ability of nicotine to induce α7 nAChR, while depletion of STAT1 resulted in enhanced induction, suggesting that nicotine might use these two transcription factors to modulate the expression of α7 nAChR in a very precise fashion. More recently, nicotine has been implicated in promoting self-renewal of stem-like side-population cells from lung cancers. Cancer stem-like cells have been implicated in tumor initiation as well as the maintenance, drug resistance, dormancy, recurrence, and metastasis of various tumor types. We had previously shown that the embryonic stem cell transcription factor, Sox2, is indispensable for self-renewal of stem-like cells from lung adenocarcinoma cell lines; hence we sought to determine whether nicotine enhances stemness of lung cancer stem-like cells through Sox2. We find that nicotine can induce the expression of Sox2 at the transcriptional level and this occurs through a nAChR-Src-Yap1-E2F1 signaling axis. Over recent years, electronic cigarettes (e-cigarettes) have emerged as healthy alternatives to traditional cigarette smoking as they do not contain tobacco; however, they do still contain nicotine. Our studies show that e-cigarette components can enhance tumor promoting properties of NSCLC cells similar to that observed with nicotine alone, and find that they can induce expression of Sox2 and mesenchymal markers as well as enhance migration and stemness of NSCLC cells. Taken together, these studies reveal novel molecular mechanisms by which exposure to nicotine, via cigarette smoke or e-cigarettes, could alter the oncogenic potential of NSCLC cells.

Subjects/Keywords: Smoking-related lung cancer; Sox2; alpha7; E2F1; Yap1; Cell Biology; Molecular Biology; Oncology

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

APA (6^th Edition):

Schaal, C. (2016). Regulation of nAChRs and Stemness by Nicotine and E-cigarettes in NSCLC. (Thesis). University of South Florida. Retrieved from https://scholarcommons.usf.edu/etd/6582

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):

Schaal, Courtney. “Regulation of nAChRs and Stemness by Nicotine and E-cigarettes in NSCLC.” 2016. Thesis, University of South Florida. Accessed January 16, 2021. https://scholarcommons.usf.edu/etd/6582.

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

MLA Handbook (7^th Edition):

Schaal, Courtney. “Regulation of nAChRs and Stemness by Nicotine and E-cigarettes in NSCLC.” 2016. Web. 16 Jan 2021.

Vancouver:

Schaal C. Regulation of nAChRs and Stemness by Nicotine and E-cigarettes in NSCLC. [Internet] [Thesis]. University of South Florida; 2016. [cited 2021 Jan 16]. Available from: https://scholarcommons.usf.edu/etd/6582.

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

Council of Science Editors:

Schaal C. Regulation of nAChRs and Stemness by Nicotine and E-cigarettes in NSCLC. [Thesis]. University of South Florida; 2016. Available from: https://scholarcommons.usf.edu/etd/6582

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

10. F. Bavo. SUBTYPE-SELECTIVE NEURONAL NICOTINIC ACETYLCHOLINE RECEPTOR AGONISTS AND ANTAGONISTS.

Degree: 2019, Università degli Studi di Milano

URL: http://hdl.handle.net/2434/607332

► This PhD thesis focuses on two specific targets, belonging to the same receptor class of Nicotinic Acetylcholine Receptors (nAChRs): the α4β2 subtype and the α7… (more)

▼ This PhD thesis focuses on two specific targets, belonging to the same receptor class of Nicotinic Acetylcholine Receptors (nAChRs): the α4β2 subtype and the α7 subtype. This elaborate is divided in two parts. The aim of the first part is the design and synthesis of α4β2 selective partial agonists as potential smoking-cessation agents. The aim of the second part is the design and synthesis of α7 antagonists with mitocan properties as antitumoral agents. Part 1. In the first project, a series of 3-nitrophenyl ethers and 3-hydroxyphenyl ethers of (S)-N-methylprolinol bearing bulky and lipophilic substituents at the C5 were designed, synthesized and assayed as putative selective α4β2 ligands. Two of them, 5-substituted with a 6-hydroxy-1-hexynyl, had high α4β2 affinity and increased α4β2/α3β4 selectivity when compared with the correspondent unsubstituted parent compounds. In the second project, each -CH= of the unselective antagonist (S,R)-N-methyl-2-pyrrolidinyl-1,4-benzodioxane and of its epimer at the benzodioxane stereocenter, was replaced by a nitrogen. The resulting four diastereomeric pairs of pyrrolidinyl-pyridodioxanes, also designed as the product of rigidification of the flexible scaffolds of pyridyl ethers of N-methyl prolinol, were studied for their nicotinic affinity at the α4β2 and α3β4. The isosteric -CH= to N substitution was detrimental for all the compounds, with the only exception of N-Methyl-pyrrolidinyl 5-pyridodioxane, with the nitrogen at position 5. Indeed, this ligand had similar affinity to its benzodioxane parent compound, but it had high α4β2/α3β4 selectivity and it was shown to be a selective partial agonist. In the third project, the unselective antagonist (S,R)-N-methyl-2-pyrrolidinyl-1,4-benzodioxane and of its epimer at the benzodioxane stereocenter were substituted at position 5 of the benzodioxane moiety, to explore the possibility of introducing selectivity and/or partial agonist as previously done with -CH= to N replacement. Among the synthesized compounds, (S,S)-N-Methyl-pyrrolidinyl-5-amino-benzodioxane had slightly improved affinity at the α4β2 affinity and highly enhanced α4β2/α3β4 selectivity than the unsubstituted parent compound, and it was shown to be a very potent partial agonist. In the fourth project, we applied computational techniques to support the interpretation of the biological results regarding N-Methyl-pyrrolidinyl 5-substituted benzodioxanes and pyridodioxanes. From these findings, we suggested that partial agonism and α4β2/α3β4 selectivity could be achieved when the benzodioxane scaffold is appropriately substituted with an HBA/HBD system, that can displace a water molecule from a small and hydrophilic subpocket of the binding site. Part 2. Adenocarcinoma and glioblastoma cell lines express α7 and α9-α10 nAChRs, whose activation promotes tumor cells growth. On these cells, the triethylammoniumethyl ether of 4-stilbenol MG624, a known selective antagonist of α7 and α9-α10 nAChRs, has antiproliferative activity. The structural analogy of MG624 with… Advisors/Committee Members: supervisor: C. Bolchi, co-supervisor: M. Pallavicini, Coordinator: G. Aldini, supervisor: C. Gotti, supervisor: B. Frølund, supervisor: K. Harpsøe, BOLCHI, CRISTIANO, PALLAVICINI, MARCO, ALDINI, GIANCARLO.

Subjects/Keywords: nicotinic acetylcholine receptors; alpha7; alpha4beta2; alpha9; glioblastoma; nicotine addiction; nicotinic partial agonists; nicotinic antagonists; Settore CHIM/08 - Chimica Farmaceutica

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

APA (6^th Edition):

Bavo, F. (2019). SUBTYPE-SELECTIVE NEURONAL NICOTINIC ACETYLCHOLINE RECEPTOR AGONISTS AND ANTAGONISTS. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/607332

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):

Bavo, F.. “SUBTYPE-SELECTIVE NEURONAL NICOTINIC ACETYLCHOLINE RECEPTOR AGONISTS AND ANTAGONISTS.” 2019. Thesis, Università degli Studi di Milano. Accessed January 16, 2021. http://hdl.handle.net/2434/607332.

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

MLA Handbook (7^th Edition):

Bavo, F.. “SUBTYPE-SELECTIVE NEURONAL NICOTINIC ACETYLCHOLINE RECEPTOR AGONISTS AND ANTAGONISTS.” 2019. Web. 16 Jan 2021.

Vancouver:

Bavo F. SUBTYPE-SELECTIVE NEURONAL NICOTINIC ACETYLCHOLINE RECEPTOR AGONISTS AND ANTAGONISTS. [Internet] [Thesis]. Università degli Studi di Milano; 2019. [cited 2021 Jan 16]. Available from: http://hdl.handle.net/2434/607332.

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

Council of Science Editors:

Bavo F. SUBTYPE-SELECTIVE NEURONAL NICOTINIC ACETYLCHOLINE RECEPTOR AGONISTS AND ANTAGONISTS. [Thesis]. Università degli Studi di Milano; 2019. Available from: http://hdl.handle.net/2434/607332

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

Virginia Commonwealth University

11. Alwassil, Osama. Small Molecules as Negative Allosteric Modulators of Alpha7 nAChRs.

Degree: MS, Pharmaceutical Sciences, 2012, Virginia Commonwealth University

URL: https://doi.org/10.25772/K30N-4834 ; https://scholarscompass.vcu.edu/etd/2829

► Alpha7 Neuronal nicotinic acetylcholine receptors (nAChRs) are involved in essential physiological functions and play a role in disorders such as Alzheimer’s disease. MD-354 (3-chlorophenylguanidine; 21),… (more)

Subjects/Keywords: Small Molecules; Negative Allosteric Modulators; NAM; nAChRs; Allosteric Modulators; Alpha7; Medicine and Health Sciences; Pharmacy and Pharmaceutical Sciences

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

APA (6^th Edition):

Alwassil, O. (2012). Small Molecules as Negative Allosteric Modulators of Alpha7 nAChRs. (Thesis). Virginia Commonwealth University. Retrieved from https://doi.org/10.25772/K30N-4834 ; https://scholarscompass.vcu.edu/etd/2829

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):

Alwassil, Osama. “Small Molecules as Negative Allosteric Modulators of Alpha7 nAChRs.” 2012. Thesis, Virginia Commonwealth University. Accessed January 16, 2021. https://doi.org/10.25772/K30N-4834 ; https://scholarscompass.vcu.edu/etd/2829.

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

MLA Handbook (7^th Edition):

Alwassil, Osama. “Small Molecules as Negative Allosteric Modulators of Alpha7 nAChRs.” 2012. Web. 16 Jan 2021.

Vancouver:

Alwassil O. Small Molecules as Negative Allosteric Modulators of Alpha7 nAChRs. [Internet] [Thesis]. Virginia Commonwealth University; 2012. [cited 2021 Jan 16]. Available from: https://doi.org/10.25772/K30N-4834 ; https://scholarscompass.vcu.edu/etd/2829.

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

Council of Science Editors:

Alwassil O. Small Molecules as Negative Allosteric Modulators of Alpha7 nAChRs. [Thesis]. Virginia Commonwealth University; 2012. Available from: https://doi.org/10.25772/K30N-4834 ; https://scholarscompass.vcu.edu/etd/2829

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

Northeastern University

12. Duggirala, Vasantha. Novel covalent probes for mapping α7 nicotinic acetylcholine receptor allosteric site/s; Novel covalent probes for mapping alpha7 nicotinic acetylcholine receptor allosteric site/s.

Degree: MS, School of Pharmacy, 2014, Northeastern University

URL: http://hdl.handle.net/2047/D20196780

► α7-nicotinic acetylcholine receptor (nAChRs), members of ligand-gated ion channels are becoming attractive targets considering their therapeutic potential for the treatment of cognitive deficits associated with… (more)

▼ α7-nicotinic acetylcholine receptor (nAChRs), members of ligand-gated ion channels are becoming attractive targets considering their therapeutic potential for the treatment of cognitive deficits associated with schizophrenia, Alzheimer's Disease (AD), Parkinson's disease, and attention-deficit/hyperactivity disorders (ADHD), as well as inflammation and neuropathic pain. α7 nAChRs can be activated either by ligands binding at orthosteric site or allosteric site/s along with enhancing the agonist evoked response. But, activation via orthosteric site caused rapid desensitization of the receptors upon exposure to agonist for prolonged time, also under diseased condition like AD the endogenous cholinergic tone is reduced. As an alternative approach, allosteric potentiators are being emphasized. These allosteric ligands regulate nicotinic cholinergic neurotransmission either in a positive or a negative way by binding to a site distinct from orthosteric site. Some of them only potentiate agonist-evoked responses (Type I) while others potentiate responses as well as decrease desensitization kinetics of the receptors (Type II). Among the Type II positive allosteric modulators (PAMs) of α7 nAChRs, 4BP-TQS (4-(4-bromophenyl)-3a,4,5,9b-tetrahydro-3H-cyclopenta[c]quinoline-8-sulfonamide) was found to have unique allosteric agonist activity in addition to being a potent PAM. It increased the scope of allosteric approach to a higher level. But with the lack of knowledge about structural features of ligand-receptor binding site, it is difficult to design potent and efficacious ligands. Mechanism of action, location of binding site and amino acids interacting at the site are all under question. As the α7 crystal structure is not available, alternative methods are being considered to discover the structural features. One of the most reliable alternatives being the use of covalent probes, this approach was taken ahead using 4BP-TQS scaffold. Covalent probes can be derived by incorporating reactive groups at the judiciously selected positions of the allosteric ligands to help determine the amino acids involved in the binding of the molecule and their role in the activity can be deduced. Photoreactive groups such as a azido or trifluoromethyl diazirine as well as electrophilic groups such as isothiocyanate were incorporated at the para-position to the phenyl ring of 4BP-TQS which was demonstrated to be a critical position for ago-PAM activity. Identifying key amino acids would aid in mapping the allosteric binding site of 7 nAChRs. Radio-labeled ligands have always been effective tools in understanding ligand-receptor interactions like binding, affinity, etc. Radio-labelled ligands at orthosteric site have been developed and successfully used in research based on acetylcholine receptor binding protein's crystal structure. In this work, I have also synthesized a radioiodinated analog (¹²⁵I) of the active enantiomer (GAT164) of 4IPTQS, a potent ago-PAM of a7 nAChR to study the drug-receptor binding interactions at this distinct…

Subjects/Keywords: alpha7-nicotinic acetylcholine receptor; covalent probe; drug-receptor; Nicotinic receptors; Therapeutic use; Molecular probes; Allosteric regulation; Ligands; Drug receptors; Amino acids

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

APA (6^th Edition):

Duggirala, V. (2014). Novel covalent probes for mapping α7 nicotinic acetylcholine receptor allosteric site/s; Novel covalent probes for mapping alpha7 nicotinic acetylcholine receptor allosteric site/s. (Masters Thesis). Northeastern University. Retrieved from http://hdl.handle.net/2047/D20196780

Chicago Manual of Style (16^th Edition):

Duggirala, Vasantha. “Novel covalent probes for mapping α7 nicotinic acetylcholine receptor allosteric site/s; Novel covalent probes for mapping alpha7 nicotinic acetylcholine receptor allosteric site/s.” 2014. Masters Thesis, Northeastern University. Accessed January 16, 2021. http://hdl.handle.net/2047/D20196780.

MLA Handbook (7^th Edition):

Duggirala, Vasantha. “Novel covalent probes for mapping α7 nicotinic acetylcholine receptor allosteric site/s; Novel covalent probes for mapping alpha7 nicotinic acetylcholine receptor allosteric site/s.” 2014. Web. 16 Jan 2021.

Vancouver:

Duggirala V. Novel covalent probes for mapping α7 nicotinic acetylcholine receptor allosteric site/s; Novel covalent probes for mapping alpha7 nicotinic acetylcholine receptor allosteric site/s. [Internet] [Masters thesis]. Northeastern University; 2014. [cited 2021 Jan 16]. Available from: http://hdl.handle.net/2047/D20196780.

Council of Science Editors:

Duggirala V. Novel covalent probes for mapping α7 nicotinic acetylcholine receptor allosteric site/s; Novel covalent probes for mapping alpha7 nicotinic acetylcholine receptor allosteric site/s. [Masters Thesis]. Northeastern University; 2014. Available from: http://hdl.handle.net/2047/D20196780

13. Ingram, Norianne Theresa. Expression of alpha 7 integrin mediates the effects of laminin on Olfactory Ensheathing Cells.

Degree: Physiological Science, 2013, UCLA

URL: http://www.escholarship.org/uc/item/4pv7h1d9

► Olfactory ensheathing cells (OECs) are unique glia found only in the olfactory system. OECs support neuronal turnover and axon outgrowth in adults and represent a… (more)

Subjects/Keywords: Physiology; Neurosciences; Cellular biology; alpha7; integrin; laminin; migration; OEC; olfactory

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APA (6^th Edition):

Ingram, N. T. (2013). Expression of alpha 7 integrin mediates the effects of laminin on Olfactory Ensheathing Cells. (Thesis). UCLA. Retrieved from http://www.escholarship.org/uc/item/4pv7h1d9

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):

Ingram, Norianne Theresa. “Expression of alpha 7 integrin mediates the effects of laminin on Olfactory Ensheathing Cells.” 2013. Thesis, UCLA. Accessed January 16, 2021. http://www.escholarship.org/uc/item/4pv7h1d9.

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

MLA Handbook (7^th Edition):

Ingram, Norianne Theresa. “Expression of alpha 7 integrin mediates the effects of laminin on Olfactory Ensheathing Cells.” 2013. Web. 16 Jan 2021.

Vancouver:

Ingram NT. Expression of alpha 7 integrin mediates the effects of laminin on Olfactory Ensheathing Cells. [Internet] [Thesis]. UCLA; 2013. [cited 2021 Jan 16]. Available from: http://www.escholarship.org/uc/item/4pv7h1d9.

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

Council of Science Editors:

Ingram NT. Expression of alpha 7 integrin mediates the effects of laminin on Olfactory Ensheathing Cells. [Thesis]. UCLA; 2013. Available from: http://www.escholarship.org/uc/item/4pv7h1d9

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

University of Georgia

14. Doad, Gurbir Singh. Synthesis and evaluation of alpha 7 nicotinic agonists as neuroprotective agents.

Degree: 2014, University of Georgia

URL: http://hdl.handle.net/10724/22095

► Alzheimer’s disease is an irreversible neurodegenerative disease, characterized by cognitive decline and loss of memory. Although a number of neurotransmitters are affected, the loss of… (more)

Subjects/Keywords: Alzheimer\'s disease; acetylcholinestrase; neuroprotective; alpha7 nicotinic receptors; N-substituted benzyl-N-methyl ethanolamines; N-benzyl-N-hydroxyethyl piperazines; PC12 cells; ED50

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APA (6^th Edition):

Doad, G. S. (2014). Synthesis and evaluation of alpha 7 nicotinic agonists as neuroprotective agents. (Thesis). University of Georgia. Retrieved from http://hdl.handle.net/10724/22095

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):

Doad, Gurbir Singh. “Synthesis and evaluation of alpha 7 nicotinic agonists as neuroprotective agents.” 2014. Thesis, University of Georgia. Accessed January 16, 2021. http://hdl.handle.net/10724/22095.

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

MLA Handbook (7^th Edition):

Doad, Gurbir Singh. “Synthesis and evaluation of alpha 7 nicotinic agonists as neuroprotective agents.” 2014. Web. 16 Jan 2021.

Vancouver:

Doad GS. Synthesis and evaluation of alpha 7 nicotinic agonists as neuroprotective agents. [Internet] [Thesis]. University of Georgia; 2014. [cited 2021 Jan 16]. Available from: http://hdl.handle.net/10724/22095.

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

Council of Science Editors:

Doad GS. Synthesis and evaluation of alpha 7 nicotinic agonists as neuroprotective agents. [Thesis]. University of Georgia; 2014. Available from: http://hdl.handle.net/10724/22095

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

University of Helsinki

15. Nousiainen, Sini. Levodopan aiheuttamien dyskinesioiden nykyiset ja kehitteillä olevat hoitomuodot.

Degree: Farmaceutiska fakulteten, 2016, University of Helsinki

URL: http://hdl.handle.net/10138/159465

► Parkinsonin tauti on etenevä, hermostoa rappeuttava sairaus, joka johtuu pääasiallisesti dopamiinihermosolujen kuolemasta aivojen mustatumakkeessa. Dopamiinivaje aiheuttaa Parkinsonin taudille tyypilliset motoriset oireet, joiden hoidon kulmakivi on… (more)

▼ Parkinsonin tauti on etenevä, hermostoa rappeuttava sairaus, joka johtuu pääasiallisesti dopamiinihermosolujen kuolemasta aivojen mustatumakkeessa. Dopamiinivaje aiheuttaa Parkinsonin taudille tyypilliset motoriset oireet, joiden hoidon kulmakivi on levodopa ja sen vaikutusta tehostavat lääkeaineet. Pitkäaikainen levodopahoito aiheuttaa usein noin 4-6 vuoden kuluttua hoidon aloituksesta tahdosta riippumattomia liikkeitä eli dyskinesioita (engl. levodopa-induced dyskinesia, LID), jotka heikentävät merkittävästi hoidosta saatavaa hyötyä. Tehokkain hoito LIDoireisiin on aivojen syvien osien sähköinen stimulaatio, mutta invasiivisena menetelmänä sen käyttö on rajattua. Tällä hetkellä ainoa myyntiluvallinen lääkevalmiste LID-oireisiin on amantadiini, jonka teho saattaa tosin heikentyä osalla potilaista jopa alle vuoden kuluttua hoidon aloittamisesta. LID-oireiden patofysiologia on hyvin monimuotoinen ja käsittää useiden eri hermovälittäjäainejärjestelmien toimintahäiriötä niin tyvitumakkeiden ympärillä kuin niiden ulkopuolella. Kolinergiseen järjestelmään kuuluvista nikotiinireseptoreista on tehty useita tutkimuksia, joissa niillä on havaittu olevan merkitystä LID-oireiden kehittymisessä. Nikotiinin kuin myös useiden sen kaltaisten yhdisteiden on havaittu vähentävän LID-oireita prekliinisissä tutkimuksissa, joista nikotiinia on tutkittu myös kliinisessä faasi II -vaiheen tutkimuksessa. Erilaisista nikotiinireseptorialayksiköistä muun muassa α7-reseptori vaikuttaa potentiaaliselta LID-oireiden hoidon kohteelta. On havaittu, että α7-reseptorin suhteen poistogeenisillä hiirillä LID-oireet lisääntyvät, mikä viittaa α7-reseptorin LID-oireilta suojaavaan vaikutukseen. Tätä käsitystä vahvistavat tutkimukset α7-nikotiinireseptoriagonistilla (ABT-107), jonka on havaittu suojaavan rottien dopamiinisoluja solutuholta ja todettu lievittävän LID-oireita apinoilla. Edellä mainittuihin havaintoihin perustuen tässä erikoistyössä tutkittiin uuden α7-nikotiinireseptoriagonistin (AZD0328) vaikutuksia LID-oireisiin hiirillä Parkinsonin taudin 6-hydroksidopamiini-(6-OHDA)-mallissa. C57BL/6J-hiirikannan naarashiirille (n=17) injektioitiin 6-OHDA-liuosta (3 µg) oikean aivopuoliskon keskimmäiseen etuaivopunokseen (engl. medial forebrain bundle, MFB). Dopamiinihermosoluvaurion onnistumista testattiin motoriikkaa mittaavan testin (kiihtyvällä nopeudella pyörivä sauva) sekä amfetamiinilla (2,5 mg/kg, i.p.) aiheutetun pyörimiskäyttäytymiskokeen avulla kahden viikon kuluttua 6-OHDA-injektiosta. Krooninen levodopakäsittely (4,5 mg/kg, s.c.) toteutettiin neljänä ensimmäisenä päivänä kaksi kertaa päivässä, minkä jälkeen käsittelyä jatkettiin kerran päivässä, päivittäin (ma-su) lopetuspäivään asti. Ennen ensimmäistä koepäivää hiirille injektoitiin yhteensä 10 päivää levodopaa. Esikäsittely (AZD0328 0,06; 0,19; 1,9 mg/kg tai 0,9 % NaCl-liuos, s.c.) annettiin 30 min ennen levodopaa. Kukin eläin sai kaikkia tutkittavia annoksia (engl. within subject design) kolmen viikon aikana neljänä eri koepäivänä. Hiiriä videoitiin minuutin ajan aina 20, 40, 60, 80 ja…

Subjects/Keywords: 6-OHDA; MFB; AZD0328; nAChR; Parkinson's disease; levodopa-induced dyskinesia; alpha7 agonist; Parkinsonin tauti; levodopan aiheuttamat dyskinesiat; nikotiinireseptori; alfa-7-agonisti; Farmakologi; Pharmacology; Farmakologia

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

APA (6^th Edition):

Nousiainen, S. (2016). Levodopan aiheuttamien dyskinesioiden nykyiset ja kehitteillä olevat hoitomuodot. (Masters Thesis). University of Helsinki. Retrieved from http://hdl.handle.net/10138/159465

Chicago Manual of Style (16^th Edition):

Nousiainen, Sini. “Levodopan aiheuttamien dyskinesioiden nykyiset ja kehitteillä olevat hoitomuodot.” 2016. Masters Thesis, University of Helsinki. Accessed January 16, 2021. http://hdl.handle.net/10138/159465.

MLA Handbook (7^th Edition):

Nousiainen, Sini. “Levodopan aiheuttamien dyskinesioiden nykyiset ja kehitteillä olevat hoitomuodot.” 2016. Web. 16 Jan 2021.

Vancouver:

Nousiainen S. Levodopan aiheuttamien dyskinesioiden nykyiset ja kehitteillä olevat hoitomuodot. [Internet] [Masters thesis]. University of Helsinki; 2016. [cited 2021 Jan 16]. Available from: http://hdl.handle.net/10138/159465.

Council of Science Editors:

Nousiainen S. Levodopan aiheuttamien dyskinesioiden nykyiset ja kehitteillä olevat hoitomuodot. [Masters Thesis]. University of Helsinki; 2016. Available from: http://hdl.handle.net/10138/159465

16. Bortz, David Michael. Positive Allosteric Modulators of the Alpha7 Nicotinic Acetylcholine Receptor Potentiate Glutamate in Prefrontal Cortex: In Vivo Evidence for a Novel Class of Schizophrenia Treatments.

Degree: PhD, Psychology, 2015, The Ohio State University

URL: http://rave.ohiolink.edu/etdc/view?acc_num=osu1429111729

► The cognitive deficits of schizophrenia are the core symptom class of the disease, but they remain largely untreated by current pharmacotherapeutic strategies. Initiatives by the… (more)

▼ The cognitive deficits of schizophrenia are the core symptom class of the disease, but they remain largely untreated by current pharmacotherapeutic strategies. Initiatives by the NIMH, such as MATRICS, have highlighted the alpha7 nicotinic acetylcholine (alpha7) receptor as a leading target for the development of novel cognition-enhancing treatments due to its unique ability to modulate many key executive function-related neurotransmitter systems, its theorized role in the portrayal of the cognitive symptoms of schizophrenia, and its agonist’s ability to reverse such deficits in preclinical models of schizophrenia. However, clinical trials conducted with several alpha7 agonists have produced mixed results. Some have theorized that these heterogeneous results in clinical trials may be caused by the indiscriminate, temporally- disengaged activation produced by direct agonists. Positive allosteric modulators (PAMs) potentiate afferent signaling without carrying any intrinsic activity, thus enhancing receptor function without mistimed, false signals. This mechanism may be more conducive to improving executive functioning, but there is a paucity of data to support this claim. Early studies in vitro indicate that alpha7 PAMs do indeed potentiate excitatory post-synaptic potentials without directly activating receptors, but no studies have tested this in vivo. The purpose of this project was to address this need by determining if two novel alpha7 PAMs would be able to potentiate glutamate release in PFC (as measured by the glutamate-sensitive microelectrode array; MEA) as a function of and dependent upon afferent stimulation. This experiment required an assay where glutamate release in the PFC was driven by afferent activation (choline) at the site where the PAMs are active (the alpha7 receptor). The mesolimbic stimulation assay, which involves stimulating the shell of the nucleus accumbens (NAcSh) with NMDA and had previously been shown to result in the dose-dependent release of glutamate in PFC (Bortz et al., 2014), was shown to also produce dose dependent increases in choline in PFC (chapter 3). Additionally, the dose-dependent glutamate increases are driven locally in PFC via cholinergic activation of the alpha7 receptor (chapter 4). This data confirmed that the mesolimbic stimulation assay could be used to characterize the potentiating effects of two alpha7 PAMs. The results presented in this dissertation demonstrated that both type I (AVL3288) and II (PNU120596) PAMs were able to potentiate glutamate release in the PFC. Additionally, the degree of potentiation of both PAMs interacted with the level of NMDA-NAcSh stimulation (i.e. the amount of choline in the PFC, see chapter 3) and the type of PAM, and neither PAM produced any change in PFC glutamate levels in the absence of an afferent signal that increased basal choline levels. Collectively, these findings demonstrate the usefulness of the MEA and mesolimbic stimulation assay to study novel alpha7 agonists and PAMs; as well as confirm, for the first time, that… Advisors/Committee Members: Bruno, John (Advisor).

Subjects/Keywords: Neurosciences; Psychology; Schizophrenia; Prefrontal cortex; glutamate; alpha7 receptor; positive allosteric modulators

…25 Chapter 4: Mesolimbic Regulation of Glutamate Release in PFC is Mediated by Local Alpha7… …47 Chapter 5: Positive Allosteric Modulators of the Alpha7 Receptor Potentiate… …that codes for the alpha7 nicotinic acetylcholine receptor (alpha7), to an elevated… …schizophrenics also support a role of cholinergic dysfunction in schizophrenia. For example, alpha7… …of learning and memory, was NMDA receptor-dependent, and that alpha7 receptors formed…

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APA (6^th Edition):

Bortz, D. M. (2015). Positive Allosteric Modulators of the Alpha7 Nicotinic Acetylcholine Receptor Potentiate Glutamate in Prefrontal Cortex: In Vivo Evidence for a Novel Class of Schizophrenia Treatments. (Doctoral Dissertation). The Ohio State University. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=osu1429111729

Chicago Manual of Style (16^th Edition):

Bortz, David Michael. “Positive Allosteric Modulators of the Alpha7 Nicotinic Acetylcholine Receptor Potentiate Glutamate in Prefrontal Cortex: In Vivo Evidence for a Novel Class of Schizophrenia Treatments.” 2015. Doctoral Dissertation, The Ohio State University. Accessed January 16, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=osu1429111729.

MLA Handbook (7^th Edition):

Bortz, David Michael. “Positive Allosteric Modulators of the Alpha7 Nicotinic Acetylcholine Receptor Potentiate Glutamate in Prefrontal Cortex: In Vivo Evidence for a Novel Class of Schizophrenia Treatments.” 2015. Web. 16 Jan 2021.

Vancouver:

Bortz DM. Positive Allosteric Modulators of the Alpha7 Nicotinic Acetylcholine Receptor Potentiate Glutamate in Prefrontal Cortex: In Vivo Evidence for a Novel Class of Schizophrenia Treatments. [Internet] [Doctoral dissertation]. The Ohio State University; 2015. [cited 2021 Jan 16]. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=osu1429111729.

Council of Science Editors:

Bortz DM. Positive Allosteric Modulators of the Alpha7 Nicotinic Acetylcholine Receptor Potentiate Glutamate in Prefrontal Cortex: In Vivo Evidence for a Novel Class of Schizophrenia Treatments. [Doctoral Dissertation]. The Ohio State University; 2015. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=osu1429111729

East Tennessee State University

17. Chandley, Michelle Johnson. Elucidating the Role of the α7 Nicotinic Receptor in the Etiology of Schizophrenia.

Degree: PhD, Biomedical Sciences, 2008, East Tennessee State University

URL: https://dc.etsu.edu/etd/1995

► The α7 subunit of the nicotinic receptor, a ligand gated ion channel with an affinity for nicotine, has long been implicated in the pathophysiology… (more)

Subjects/Keywords: alpha7 subunit nicotinic receptor; schizophrenia; autoantibody; CREB; Life Sciences; Medicine and Health Sciences; Mental Disorders; Molecular and Cellular Neuroscience; Neuroscience and Neurobiology; Psychiatry and Psychology

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APA (6^th Edition):

Chandley, M. J. (2008). Elucidating the Role of the α7 Nicotinic Receptor in the Etiology of Schizophrenia. (Doctoral Dissertation). East Tennessee State University. Retrieved from https://dc.etsu.edu/etd/1995

Chicago Manual of Style (16^th Edition):

Chandley, Michelle Johnson. “Elucidating the Role of the α7 Nicotinic Receptor in the Etiology of Schizophrenia.” 2008. Doctoral Dissertation, East Tennessee State University. Accessed January 16, 2021. https://dc.etsu.edu/etd/1995.

MLA Handbook (7^th Edition):

Chandley, Michelle Johnson. “Elucidating the Role of the α7 Nicotinic Receptor in the Etiology of Schizophrenia.” 2008. Web. 16 Jan 2021.

Vancouver:

Chandley MJ. Elucidating the Role of the α7 Nicotinic Receptor in the Etiology of Schizophrenia. [Internet] [Doctoral dissertation]. East Tennessee State University; 2008. [cited 2021 Jan 16]. Available from: https://dc.etsu.edu/etd/1995.

Council of Science Editors:

Chandley MJ. Elucidating the Role of the α7 Nicotinic Receptor in the Etiology of Schizophrenia. [Doctoral Dissertation]. East Tennessee State University; 2008. Available from: https://dc.etsu.edu/etd/1995

18. Lutz, Joseph A. Flavonoids with Novel Nicotinic Activity as Potential Pharmacotherapies to Treat Ethanol-Induced Neurotoxicity.

Degree: 2014, University of Kentucky

URL: https://uknowledge.uky.edu/pharmacy_etds/43

► Ethanol causes neurotoxicity via several mechanisms at different points in the cycle of dependence, including neuroinflammation and oxidative stress during ethanol exposure as well as… (more)

Subjects/Keywords: ethanol-induced neurotoxicity; neuroinflammation; excitotoxicity; alpha7 nicotinic acetylcholine receptor; rhamnetin; Molecular and Cellular Neuroscience; Natural Products Chemistry and Pharmacognosy; Pharmacology

…the alpha7 nicotinic acetylcholine receptor which has emerged as a pluripotent target for… …alpha4-beta2 heteromeric nAChRs and the alpha7 homomeric nAChRs. Alpha7 nAChRs are discreetly… …alpha7 nAChRs have been found on non-neuronal cells such as macrophages [86]… …astrocytes [87], and microglia [88]. Thus, alpha7 nAChRs are present on neurons… …potential to attenuate neuroinflammation and excitotoxicity. 1.4.1 Alpha7 nAChR activation on…

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APA (6^th Edition):

Lutz, J. A. (2014). Flavonoids with Novel Nicotinic Activity as Potential Pharmacotherapies to Treat Ethanol-Induced Neurotoxicity. (Doctoral Dissertation). University of Kentucky. Retrieved from https://uknowledge.uky.edu/pharmacy_etds/43

Chicago Manual of Style (16^th Edition):

Lutz, Joseph A. “Flavonoids with Novel Nicotinic Activity as Potential Pharmacotherapies to Treat Ethanol-Induced Neurotoxicity.” 2014. Doctoral Dissertation, University of Kentucky. Accessed January 16, 2021. https://uknowledge.uky.edu/pharmacy_etds/43.

MLA Handbook (7^th Edition):

Lutz, Joseph A. “Flavonoids with Novel Nicotinic Activity as Potential Pharmacotherapies to Treat Ethanol-Induced Neurotoxicity.” 2014. Web. 16 Jan 2021.

Vancouver:

Lutz JA. Flavonoids with Novel Nicotinic Activity as Potential Pharmacotherapies to Treat Ethanol-Induced Neurotoxicity. [Internet] [Doctoral dissertation]. University of Kentucky; 2014. [cited 2021 Jan 16]. Available from: https://uknowledge.uky.edu/pharmacy_etds/43.

Council of Science Editors:

Lutz JA. Flavonoids with Novel Nicotinic Activity as Potential Pharmacotherapies to Treat Ethanol-Induced Neurotoxicity. [Doctoral Dissertation]. University of Kentucky; 2014. Available from: https://uknowledge.uky.edu/pharmacy_etds/43

19. Souza, Anelise Cristina Parras de, 1983-. Modulação da expressão do receptor colinérgico tipo alpha7 por dieta hiperlipídica : implicações para a resposta inflamatória = Modulation of alpha7 type cholinergic receptor expression by hyperlipidic diet: implications for the inflammatory response: Modulation of alpha7 type cholinergic receptor expression by hyperlipidic diet : implications for the inflammatory response.

Degree: 2018, Universidade Estadual de Campinas

URL: http://repositorio.unicamp.br/jspui/handle/REPOSIP/333028

► Abstract: Sepsis is one of the leading causes of death in hospitalized patients, and the chronic and low-grade inflammation observed in obesity is a major… (more)

Subjects/Keywords: Receptor nicotínico de acetilcolina alfa7; Inflamação; Dieta hiperlipídica; Hipotálamo; Sistema imunológico; Alpha7 nicotinic acetylcholine receptor; Inflammation; Diet high fat; Hypothalamus; Immune system

…tissues, contributing to a higher probability of death in sepsis. Keywords: Alpha7 nicotinic…

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APA (6^th Edition):

Souza, Anelise Cristina Parras de, 1. (2018). Modulação da expressão do receptor colinérgico tipo alpha7 por dieta hiperlipídica : implicações para a resposta inflamatória = Modulation of alpha7 type cholinergic receptor expression by hyperlipidic diet: implications for the inflammatory response: Modulation of alpha7 type cholinergic receptor expression by hyperlipidic diet : implications for the inflammatory response. (Thesis). Universidade Estadual de Campinas. Retrieved from http://repositorio.unicamp.br/jspui/handle/REPOSIP/333028

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):

Souza, Anelise Cristina Parras de, 1983-. “Modulação da expressão do receptor colinérgico tipo alpha7 por dieta hiperlipídica : implicações para a resposta inflamatória = Modulation of alpha7 type cholinergic receptor expression by hyperlipidic diet: implications for the inflammatory response: Modulation of alpha7 type cholinergic receptor expression by hyperlipidic diet : implications for the inflammatory response.” 2018. Thesis, Universidade Estadual de Campinas. Accessed January 16, 2021. http://repositorio.unicamp.br/jspui/handle/REPOSIP/333028.

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

MLA Handbook (7^th Edition):

Souza, Anelise Cristina Parras de, 1983-. “Modulação da expressão do receptor colinérgico tipo alpha7 por dieta hiperlipídica : implicações para a resposta inflamatória = Modulation of alpha7 type cholinergic receptor expression by hyperlipidic diet: implications for the inflammatory response: Modulation of alpha7 type cholinergic receptor expression by hyperlipidic diet : implications for the inflammatory response.” 2018. Web. 16 Jan 2021.

Vancouver:

Souza, Anelise Cristina Parras de 1. Modulação da expressão do receptor colinérgico tipo alpha7 por dieta hiperlipídica : implicações para a resposta inflamatória = Modulation of alpha7 type cholinergic receptor expression by hyperlipidic diet: implications for the inflammatory response: Modulation of alpha7 type cholinergic receptor expression by hyperlipidic diet : implications for the inflammatory response. [Internet] [Thesis]. Universidade Estadual de Campinas; 2018. [cited 2021 Jan 16]. Available from: http://repositorio.unicamp.br/jspui/handle/REPOSIP/333028.

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

Council of Science Editors:

Souza, Anelise Cristina Parras de 1. Modulação da expressão do receptor colinérgico tipo alpha7 por dieta hiperlipídica : implicações para a resposta inflamatória = Modulation of alpha7 type cholinergic receptor expression by hyperlipidic diet: implications for the inflammatory response: Modulation of alpha7 type cholinergic receptor expression by hyperlipidic diet : implications for the inflammatory response. [Thesis]. Universidade Estadual de Campinas; 2018. Available from: http://repositorio.unicamp.br/jspui/handle/REPOSIP/333028

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

20. Gould, Timothy M. Non-Ionotropic Nicotinic Acetylcholine Receptor Signaling.

Degree: PhD, Chemistry, 2016, University of Florida

URL: https://ufdc.ufl.edu/UFE0050365

► Transmembrane receptors like those sensitive to acetylcholine are typically classified as either ionotropic or metabotropic with respect to their cellular function. However, studies indicate there… (more)

▼ Transmembrane receptors like those sensitive to acetylcholine are typically classified as either ionotropic or metabotropic with respect to their cellular function. However, studies indicate there may be non-ionotropic function(s) associated with some ligand-gated ion channels such as the nicotinic acetylcholine receptors (nAChR). This dissertation tests the hypothesis that non-ionotropic or metabotropic-like nAChR function(s) exist, thus the primary objective was to execute experiments that would generate data to address this hypothesis. Specifically within the context of immune cell function, alpha7 subunit-containing nAChR and the putatively associated homopentameric receptor have been implicated in the regulation of inflammation-related signal transduction activities. Currently, research on the cholinergic anti-inflammatory pathway and nAChR-dependent regulation of inflammation is somewhat confounded by the observations that while nAChR proteins have been detected in several types of immune cells, no macroscopic nAChR-dependent ionotropic function has been experimentally demonstrated in such cells. Experiments herein with human T lymphocyte cell lines (Jurkat) support the native expression of alpha7 and other nAChR subunit mRNA but the cells lack detectable ion channel function. Nonetheless, experiments with mitogen-stimulated Jurkat cells demonstrate that ligands with known activities on alpha7-containing nAChR (GTS-21 and NS6740) affect intracellular signaling including NF-kappaB activation, cytokine (IL-2) synthesis, cell survival and apoptosis. The effects of GTS-21 and NS6740 were also associated with changes in expression of nAChR subunit mRNA, including alpha7. The signaling/survival effects induced by GTS-21 and NS6740 in stimulated Jurkat cells were not blocked by an antagonist of alpha7 nAChR ion channel function, were not sensitive to a non-selective muscarinic acetylcholine receptor antagonist, and were not dependent on extracellular calcium. At high concentrations GTS-21 and NS6740 were effective regulators of such effects whereas efficacious nAChR ion channel agonists such as nicotine were not. Importantly, GTS-21 and NS6740 effects on Jurkat cell signaling were largely persistent even in putatively alpha7-deficient cells, indicating that alpha7 nAChR may not be involved in this regulation. Taken together and in conclusion, these studies suggest that GTS-21 and NS6740 may impact immune cell signaling through an alpha7 nAChR-independent, non-ionotropic mechanism. ( en ) Advisors/Committee Members: HORENSTEIN,NICOLE ALANA (committee chair), MURRAY,LESLIE JUSTIN (committee member), BUTCHER,REBECCA ANN (committee member), PAPKE,ROGER LEE (committee member).

Subjects/Keywords: Ion channels; Journalism; Messenger RNA; Nicotinic receptors; Plasmids; Receptors; RNA; Signals; T lymphocytes; Viability; acetylcholine – alpha7 – inflammation – nicotinic – non-ionotropic – receptor – signal – transduction

…Choline acetyltransferase CHRFAM7A Cholinergic receptor, nicotinic, alpha7, and family with… …Cholinergic receptor, nicotinic, alpha7 CNS Central nervous system ConA Concanavalin A 12…

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APA (6^th Edition):

Gould, T. M. (2016). Non-Ionotropic Nicotinic Acetylcholine Receptor Signaling. (Doctoral Dissertation). University of Florida. Retrieved from https://ufdc.ufl.edu/UFE0050365

Chicago Manual of Style (16^th Edition):

Gould, Timothy M. “Non-Ionotropic Nicotinic Acetylcholine Receptor Signaling.” 2016. Doctoral Dissertation, University of Florida. Accessed January 16, 2021. https://ufdc.ufl.edu/UFE0050365.

MLA Handbook (7^th Edition):

Gould, Timothy M. “Non-Ionotropic Nicotinic Acetylcholine Receptor Signaling.” 2016. Web. 16 Jan 2021.

Vancouver:

Gould TM. Non-Ionotropic Nicotinic Acetylcholine Receptor Signaling. [Internet] [Doctoral dissertation]. University of Florida; 2016. [cited 2021 Jan 16]. Available from: https://ufdc.ufl.edu/UFE0050365.

Council of Science Editors:

Gould TM. Non-Ionotropic Nicotinic Acetylcholine Receptor Signaling. [Doctoral Dissertation]. University of Florida; 2016. Available from: https://ufdc.ufl.edu/UFE0050365

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Open Access Theses and Dissertations