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Tau Filament Self-Assembly and Structure Tau as a Therapeutic Target.pdf (1.62 MB)

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

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posted on 2023-06-10, 00:59 authored by Sebastian S Oakley, Mahmoud MainaMahmoud Maina, Karen MarshallKaren Marshall, Youssra Al-Hilaly, Charlie R Harrington, Claude M Wischik, Louise SerpellLouise Serpell
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.

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Publication status

  • Published

File Version

  • Published version

Journal

Frontiers in Neurology

ISSN

1664-2295

Publisher

Frontiers

Volume

11

Page range

590754

Event location

Switzerland

Department affiliated with

  • Biochemistry Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2021-09-17

First Open Access (FOA) Date

2021-09-17

First Compliant Deposit (FCD) Date

2021-09-15

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