Doxycycline Interferes With Tau Aggregation and Reduces Its Neuronal Toxicity.
Alzheimer's disease
doxycycline
protein aggregation
tau
tauopathies
Journal
Frontiers in aging neuroscience
ISSN: 1663-4365
Titre abrégé: Front Aging Neurosci
Pays: Switzerland
ID NLM: 101525824
Informations de publication
Date de publication:
2021
2021
Historique:
received:
30
11
2020
accepted:
22
02
2021
entrez:
8
4
2021
pubmed:
9
4
2021
medline:
9
4
2021
Statut:
epublish
Résumé
Tauopathies are neurodegenerative disorders with increasing incidence and still without cure. The extensive time required for development and approval of novel therapeutics highlights the need for testing and repurposing known safe molecules. Since doxycycline impacts α-synuclein aggregation and toxicity, herein we tested its effect on tau. We found that doxycycline reduces amyloid aggregation of the 2N4R and K18 isoforms of tau protein in a dose-dependent manner. Furthermore, in a cell free system doxycycline also prevents tau seeding and in cell culture reduces toxicity of tau aggregates. Overall, our results expand the spectrum of action of doxycycline against aggregation-prone proteins, opening novel perspectives for its repurposing as a disease-modifying drug for tauopathies.
Identifiants
pubmed: 33828477
doi: 10.3389/fnagi.2021.635760
pmc: PMC8020845
doi:
Types de publication
Journal Article
Langues
eng
Pagination
635760Informations de copyright
Copyright © 2021 Medina, González-Lizárraga, Dominguez-Meijide, Ploper, Parrales, Sequeira, Cima-Omori, Zweckstetter, Del Bel, Michel, Outeiro, Raisman-Vozari, Chehín and Socias.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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