Cofilin 1 promotes the pathogenicity and transmission of pathological α-synuclein in mouse models of Parkinson's disease

作者：Yan, Mingmin; Xiong, Min; Dai, Lijun; Zhang, Xingyu; Zha, Yunhong; Deng, Xiaorong; Yu, Zhui; Zhang, Zhentao^*

来源：npj Parkinsons Disease, 2022, 8(1): 1.

DOI：10.1038/s41531-021-00272-w

• LEWY BODY
• EXTRACELLULAR VESICLES
• AGGREGATION
• DEGRADATION
• PROTEINS
• FIBRILS
• STRAINS

The pathological hallmark of Parkinson's disease (PD) is the presence of Lewy bodies (LBs) with aggregated alpha-synuclein being the major component. The abnormal alpha-synuclein aggregates transfer between cells, recruit endogenous alpha-synuclein into toxic LBs, and finally trigger neuronal injury. However, the molecular mechanisms mediating the aggregation and transmission of pathological asynuclein remain unknown. Previously we found that cofilin 1, a member of the actin-binding protein, promotes the aggregation and pathogenicity of alpha-synuclein in vitro. Here we further investigated the effect of cofilin 1 in mouse models of PD. We found that the mixed fibrils composed of cofilin 1 and alpha-synuclein are more pathogenic to mice and more prone to propagation than pure asynuclein fibrils. Overexpression of cofilin 1 enhances the seeding and spreading of alpha-synuclein aggregates, and induces PD-like behavioral impairments in mice. Together, these results illustrate the important role of cofilin 1 in the pathogenicity and transmission of alpha-synuclein during the onset and progression of PD.

• 单位
  武汉大学; 1