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
journal contribution
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 SerpellTau 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.
History
Publication status
- Published
File Version
- Published version
Journal
Frontiers in NeurologyISSN
1664-2295Publisher
FrontiersExternal DOI
Volume
11Page range
590754Event location
SwitzerlandDepartment affiliated with
- Biochemistry Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2021-09-17First Open Access (FOA) Date
2021-09-17First Compliant Deposit (FCD) Date
2021-09-15Usage metrics
Categories
No categories selectedKeywords
Licence
Exports
RefWorks
BibTeX
Ref. manager
Endnote
DataCite
NLM
DC