Tau filament self-assembly and structure: tau as a therapeutic target

Oakley, Sebastian S, Maina, Mahmoud B, Marshall, Karen E, Al-Hilaly, Youssra K, Harrington, Charlie R, Wischik, Claude M and Serpell, Louise C (2020) Tau filament self-assembly and structure: tau as a therapeutic target. Frontiers in Neurology, 11. p. 590754. ISSN 1664-2295

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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.

Item Type: Article
Keywords: Alzheimer's disease, filaments, in vitro models, self-assembly, tau, tau aggregation inhibitors, tauopathies
Schools and Departments: School of Life Sciences > Biochemistry
School of Life Sciences > Neuroscience
SWORD Depositor: Mx Elements Account
Depositing User: Mx Elements Account
Date Deposited: 17 Sep 2021 13:06
Last Modified: 17 Sep 2021 13:16
URI: http://sro.sussex.ac.uk/id/eprint/101717

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