Molecular mechanisms of Tau protein aggregation inhibition

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dc.contributor.author Akoury, Elias
dc.date.accessioned 2019-03-22T12:14:41Z
dc.date.available 2019-03-22T12:14:41Z
dc.date.copyright 2013 en_US
dc.date.issued 2019-03-22
dc.identifier.uri http://hdl.handle.net/10725/10257
dc.description.abstract Of all neurodegenerative diseases, Alzheimer´s Disease is the most widespread dementia syndrome, exhibiting progressive memory loss and intellectual abilities. One of the pathological hallmarks of this disease is associated to the presence of abundant intracellular deposits of the Tau protein. Accumulation of these stable species is a multistep process that involves the formation of various transients. Understanding this key step may eventually enable to obstruct aggregation. Tau protein is an intrinsically disordered protein, abundant in neuronal axons where it promotes and stabilizes microtubule assembly. Chapter 1 discusses the physiological function and pathological consequences of this protein and sheds light on the current Taubased research implemented in therapeutic strategies. This chapter also reviews the identification of inhibitors of Tau aggregation as potential disease-modifying drugs; with a detailed discussion of two organic compounds we have recently screened, Phthalocyanine Tetrasulfonate and Phenothiazine Methylene Blue. The same chapter then introduces the Heat shock proteins and their role in Tau clearance. The chapters that follow report our research investigation of aggregation inhibitors and chaperonic partners of Tau where we used an integrated approach to detect possible assemblies of pathogenic conformational transitions. Chapter 2 represents the Phthalocyanine tetrasulfonate study and its inhibition of Tau filament formation by conformational modulation. Chapter 3 investigates the mechanistic basis of the phenothiazine-driven inhibition of Tau aggregation. Chapter 4, examines how the imbalance of Hsp70 family variants fosters Tau accumulation. As a final point, the significance of the biophysical techniques incorporated in the three published manuscripts are briefly discussed in the last part of Chapter 1. en_US
dc.language.iso en en_US
dc.title Molecular mechanisms of Tau protein aggregation inhibition en_US
dc.type Thesis en_US
dc.author.degree Doctor of Pharmacy en_US
dc.author.school SAS en_US
dc.author.idnumber 201900590 en_US
dc.author.department Natural Sciences en_US
dc.description.embargo N/A en_US
dc.description.physdesc xvi, 240 p. ill en_US
dc.author.advisor Zweckstetter, Markus
dc.description.bibliographiccitations Includes bibliographical references en_US
dc.identifier.ctation Akoury, E. (2013). Molecular Mechanisms of Tau Protein Aggregation Inhibition (Doctoral dissertation, Niedersächsische Staats-und Universitätsbibliothek Göttingen). en_US
dc.author.email elias.akoury@lau.edu.lb en_US
dc.identifier.tou http://libraries.lau.edu.lb/research/laur/terms-of-use/thesis.php en_US
dc.identifier.url https://d-nb.info/1044870931/34 en_US
dc.orcid.id https://orcid.org/0000-0001-5202-8935 en_US
dc.publisher.institution Niedersächsische Staats-und Universitätsbibliothek Göttingen en_US
dc.author.affiliation Lebanese American University en_US

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