Tau accelerates α-synuclein aggregation and spreading in Parkinson’s disease
| Autor: | Lina Pan, Chunrui Li, Lanxia Meng, Ye Tian, Mingyang He, Xin Yuan, Guoxin Zhang, Zhaohui Zhang, Jing Xiong, Guiqin Chen, Zhentao Zhang |
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| Rok vydání: | 2022 |
| Předmět: | |
| Zdroj: | Brain. 145:3454-3471 |
| ISSN: | 1460-2156 0006-8950 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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