Al-Hilaly_et_al-2019-FEBS_Letters.pdf (1.06 MB)
Tau (297-391) forms filaments that structurally mimic the core of paired helical filaments in Alzheimer’s disease brain
journal contribution
posted on 2023-06-09, 19:49 authored by Youssra Al-Hilaly, Bronwen E Foster, Luca Biasetti, Liisa Lutter, Saskia Pollack, Janet E Rickard, John M D Storey, Charles R Harrington, Wei-Feng Xue, Claude M Wischik, Louise SerpellLouise SerpellThe constituent paired helical filaments (PHFs) in neurofibrillary tangles are insoluble intracellular deposits central to the development of Alzheimer’s disease (AD) and other tauopathies. Full-length tau requires the addition of anionic cofactors such as heparin to enhance assembly. We have shown that a fragment from the proteolytically stable core of the PHF, tau 297-391 known as ‘dGAE’, spontaneously forms cross-ß-containing PHFs and straight filaments under physiological conditions. Here, we have analysed and compared the structures of the filaments formed by dGAE in vitro with those deposited in the brains of individuals diagnosed with AD. We show that dGAE forms PHFs that share a macromolecular structure similar to those found in brain tissue. Thus, dGAEs may serve as a model system for studying core domain assembly and for screening for inhibitors of tau aggregation.
History
Publication status
- Published
File Version
- Published version
Journal
FEBS LettersISSN
0014-5793Publisher
WileyExternal DOI
Page range
1-7Department affiliated with
- Neuroscience Publications
Research groups affiliated with
- Dementia Research Group Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2019-12-03First Open Access (FOA) Date
2019-12-03First Compliant Deposit (FCD) Date
2019-12-03Usage metrics
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