Tau (297-391) forms filaments that structurally mimic the core of paired helical filaments in Alzheimer's disease brain.
Alzheimer’s disease
neurofibrillary tangles
paired helical filaments
tau
Journal
FEBS letters
ISSN: 1873-3468
Titre abrégé: FEBS Lett
Pays: England
ID NLM: 0155157
Informations de publication
Date de publication:
03 2020
03 2020
Historique:
received:
02
08
2019
revised:
21
10
2019
accepted:
23
10
2019
pubmed:
14
11
2019
medline:
6
10
2020
entrez:
14
11
2019
Statut:
ppublish
Résumé
The 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-β-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.
Identifiants
pubmed: 31721178
doi: 10.1002/1873-3468.13675
pmc: PMC7078754
doi:
Substances chimiques
MAPT protein, human
0
tau Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
944-950Subventions
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/S003312/1
Pays : United Kingdom
Informations de copyright
© 2019 The Authors. FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.
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