α-突触核蛋白
帕金森病
神经科学
疾病
医学
心理学
内科学
作者
Lina Pan,Chunrui Li,Lanxia Meng,Ye Tian,Mingyang He,Xin Yuan,Guoxin Zhang,Zhaohui Zhang,Jing Xiong,Guiqin Chen,Zhentao Zhang
出处
期刊:Brain
[Oxford University Press]
日期:2022-05-13
卷期号:145 (10): 3454-3471
被引量:35
标识
DOI:10.1093/brain/awac171
摘要
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.
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