| First Author | Pan L | Year | 2022 |
| Journal | Brain | Volume | 145 |
| Issue | 10 | Pages | 3454-3471 |
| PubMed ID | 35552614 | Mgi Jnum | J:357478 |
| Mgi Id | MGI:7748927 | Doi | 10.1093/brain/awac171 |
| Citation | Pan L, et al. (2022) Tau accelerates alpha-synuclein aggregation and spreading in Parkinson's disease. Brain 145(10):3454-3471 |
| abstractText | The aggregation and prion-like propagation of alpha-synuclein are involved in the pathogenesis of Parkinson's disease. However, the underlying mechanisms regulating the assembly and spreading of alpha-synuclein fibrils remain poorly understood. Tau co-deposits with alpha-synuclein in the brains of Parkinson's disease patients, suggesting a pathological interplay between them. Here we show that tau interacts with alpha-synuclein and accelerates its aggregation. Compared with pure alpha-synuclein fibrils, the tau-modified alpha-synuclein fibrils show enhanced seeding activity, inducing mitochondrial dysfunction, synaptic impairment and neurotoxicity in vitro. Injection of the tau-modified alpha-synuclein fibrils into the striatum of mice induces more severe alpha-synuclein pathology, motor dysfunction and cognitive impairment when compared with the mice injected with pure alpha-synuclein fibrils. Knockout of tau attenuates the propagation of alpha-synuclein pathology and Parkinson's disease-like symptoms both in mice injected with alpha-syn fibrils and alpha-syn A53T transgenic mice. In conclusion, tau facilitates alpha-synuclein aggregation and propagation in Parkinson's disease. |
