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Tau Filament Self-Assembly and Structure: Tau as a Therapeutic Target.

Authors :
Oakley SS
Maina MB
Marshall KE
Al-Hilaly YK
Harrington CR
Wischik CM
Serpell LC
Source :
Frontiers in neurology [Front Neurol] 2020 Nov 12; Vol. 11, pp. 590754. Date of Electronic Publication: 2020 Nov 12 (Print Publication: 2020).
Publication Year :
2020

Abstract

Tau plays an important pathological role in a group of neurodegenerative diseases called tauopathies, including Alzheimer's disease, Pick's disease, chronic traumatic encephalopathy and corticobasal degeneration. In each disease, tau self-assembles abnormally to form filaments that deposit in the brain. Tau is a natively unfolded protein that can adopt distinct structures in different pathological disorders. Cryo-electron microscopy has recently provided a series of structures for the core of the filaments purified from brain tissue from patients with different tauopathies and revealed that they share a common core region, while differing in their specific conformation. This structurally resolvable part of the core is contained within a proteolytically stable core region from the repeat domain initially isolated from AD tau filaments. Tau has recently become an important target for therapy. Recent work has suggested that the prevention of tau self-assembly may be effective in slowing the progression of Alzheimer's disease and other tauopathies. Here we review the work that explores the importance of tau filament structures and tau self-assembly mechanisms, as well as examining model systems that permit the exploration of the mode of action of potential inhibitors.<br /> (Copyright © 2020 Oakley, Maina, Marshall, Al-Hilaly, Harrington, Wischik and Serpell.)

Details

Language :
English
ISSN :
1664-2295
Volume :
11
Database :
MEDLINE
Journal :
Frontiers in neurology
Publication Type :
Academic Journal
Accession number :
33281730
Full Text :
https://doi.org/10.3389/fneur.2020.590754