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@PHDTHESIS{Akoury:282307,
author = {Akoury, Elias},
title = {{M}olecular {M}echanisms of {T}au {P}rotein {A}ggregation
{I}nhibition},
school = {Georg-August-Universität Göttingen},
type = {Dissertation},
reportid = {DZNE-2025-01277},
pages = {240 p.},
year = {2013},
note = {Dissertation, Georg-August-Universität Göttingen, 2013},
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
Tau-based 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.},
cin = {AG Zweckstetter},
cid = {I:(DE-2719)1410001},
pnm = {352 - Disease Mechanisms (POF4-352)},
pid = {G:(DE-HGF)POF4-352},
typ = {PUB:(DE-HGF)11},
url = {https://pub.dzne.de/record/282307},
}