Tau accelerates α-synuclein aggregation and spreading in Parkinson's disease.
Brain
; 145(10): 3454-3471, 2022 10 21.
Article
em En
| MEDLINE
| ID: mdl-35552614
ABSTRACT
The aggregation and prion-like propagation of α-synuclein are involved in the pathogenesis of Parkinson's disease. However, the underlying mechanisms regulating the assembly and spreading of α-synuclein fibrils remain poorly understood. Tau co-deposits with α-synuclein in the brains of Parkinson's disease patients, suggesting a pathological interplay between them. Here we show that tau interacts with α-synuclein and accelerates its aggregation. Compared with pure α-synuclein fibrils, the tau-modified α-synuclein fibrils show enhanced seeding activity, inducing mitochondrial dysfunction, synaptic impairment and neurotoxicity in vitro. Injection of the tau-modified α-synuclein fibrils into the striatum of mice induces more severe α-synuclein pathology, motor dysfunction and cognitive impairment when compared with the mice injected with pure α-synuclein fibrils. Knockout of tau attenuates the propagation of α-synuclein pathology and Parkinson's disease-like symptoms both in mice injected with α-syn fibrils and α-syn A53T transgenic mice. In conclusion, tau facilitates α-synuclein aggregation and propagation in Parkinson's disease.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doença de Parkinson
/
Príons
/
Sinucleinopatias
Limite:
Animals
Idioma:
En
Revista:
Brain
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
China