1. Tau accelerates α-synuclein aggregation and spreading in Parkinson's disease.
- Author
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Pan, Lina, Li, Chunrui, Meng, Lanxia, Tian, Ye, He, Mingyang, Yuan, Xin, Zhang, Guoxin, Zhang, Zhaohui, Xiong, Jing, Chen, Guiqin, and Zhang, Zhentao
- Subjects
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PRIONS , *NERVE tissue proteins , *PARKINSON'S disease , *SYNUCLEINS , *RESEARCH funding , *MICE , *ANIMALS - 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. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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