Fisetin inhibits tau aggregation by interacting with the protein and preventing the formation of β-strands.
Alzheimer's disease
Compound-protein interaction
Fisetin
Molecular dynamic simulation
Protein aggregation
Tau protein
Journal
International journal of biological macromolecules
ISSN: 1879-0003
Titre abrégé: Int J Biol Macromol
Pays: Netherlands
ID NLM: 7909578
Informations de publication
Date de publication:
01 May 2021
01 May 2021
Historique:
received:
30
01
2021
revised:
25
02
2021
accepted:
27
02
2021
pubmed:
5
3
2021
medline:
22
7
2021
entrez:
4
3
2021
Statut:
ppublish
Résumé
Alzheimer's disease is a neurodegenerative disease which severely impacts the health of the elderly. Current treatments are only able to alleviate symptoms, but not prevent or cure the disease. The neurofibrillary tangles formed by tau protein aggregation are one of the defining characteristics of Alzheimer's disease, so tau protein has become a key target for the drug design. In this study, we show that fisetin, a plant-derived polyphenol compound, can inhibit aggregation of the tau fragment, K18, and can disaggregate tau K18 filaments in vitro. Meanwhile it is able to prevent the formation of tau aggregates in cells. Both experimental and computational studies indicate that fisetin could directly interact with tau K18 protein. The binding is mainly created by hydrogen bond and van der Waal force, prevents the formation of β-strands at the two hexapeptide motifs, and does not perturb the secondary structure or the tubulin binding ability of tau protein. In summary, fisetin might be a candidate for further development as a potential preventive or therapeutic drug for Alzheimer's disease.
Identifiants
pubmed: 33662414
pii: S0141-8130(21)00511-0
doi: 10.1016/j.ijbiomac.2021.02.210
pmc: PMC9022726
mid: NIHMS1792276
pii:
doi:
Substances chimiques
Flavonols
0
MAPT protein, human
0
Protein Aggregates
0
Recombinant Proteins
0
tau Proteins
0
fisetin
OO2ABO9578
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
381-393Subventions
Organisme : NIA NIH HHS
ID : R37 AG019391
Pays : United States
Organisme : NIA NIH HHS
ID : RF1 AG066493
Pays : United States
Informations de copyright
Copyright © 2021 Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors declare no conflicts of interest in regards to this manuscript.
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