期刊
MOLECULAR NEUROBIOLOGY
卷 59, 期 2, 页码 1273-1284出版社
SPRINGER
DOI: 10.1007/s12035-021-02713-2
关键词
PD; LBs; aSyn; Aggregation; Phosphorylation
资金
- EU/EFPIA/Innovative Medicines Initiative [2] Joint Undertaking (IMPRIND) [116060]
- Galician Government (Programa de axuda a etapa posdoutoral, XUGA, GAIN) [ED481B 2017/053]
- Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) [EXC 2067/1-390729940, SFB1286]
Parkinson's disease is a neurodegenerative disorder characterized by the accumulation of misfolded alpha-synuclein. This study demonstrates that the levels of alpha-synuclein play a role in the aggregation and seeding of the protein, which may explain the selective vulnerability of different cell types in Parkinson's disease. Understanding the cellular processes involved in alpha-synuclein aggregation could lead to the development of new therapeutic strategies.
Parkinson's disease is a progressive neurodegenerative disorder characterized by the accumulation of misfolded alpha-synuclein in intraneuronal inclusions known as Lewy bodies and Lewy neurites. Multiple studies strongly implicate the levels of alpha-synuclein as a major risk factor for the onset and progression of Parkinson's disease. Alpha-synuclein pathology spreads progressively throughout interconnected brain regions but the precise molecular mechanisms underlying the seeding of alpha-synuclein aggregation are still unclear. Here, using stable cell lines expressing alpha-synuclein, we examined the correlation between endogenous alpha-synuclein levels and the seeding propensity by exogenous alpha-synuclein preformed fibrils. We applied biochemical approaches and imaging methods in stable cell lines expressing alpha-synuclein and in primary neurons to determine the impact of alpha-synuclein levels on seeding and aggregation. Our results indicate that the levels of alpha-synuclein define the pattern and severity of aggregation and the extent of p-alpha-synuclein deposition, likely explaining the selective vulnerability of different cell types in synucleinopathies. The elucidation of the cellular processes involved in the pathological aggregation of alpha-synuclein will enable the identification of novel targets and the development of therapeutic strategies for Parkinson's disease and other synucleinopathies.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据