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

Abstract

The pathological hallmark of Parkinson's disease (PD) is the presence of Lewy bodies (LBs) with aggregated α-synuclein being the major component. The abnormal α-synuclein aggregates transfer between cells, recruit endogenous α-synuclein into toxic LBs, and finally trigger neuronal injury. However, the molecular mechanisms mediating the aggregation and transmission of pathological α-synuclein remain unknown. Previously we found that cofilin 1, a member of the actin-binding protein, promotes the aggregation and pathogenicity of α-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 α-synuclein are more pathogenic to mice and more prone to propagation than pure α-synuclein fibrils. Overexpression of cofilin 1 enhances the seeding and spreading of α-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 α-synuclein during the onset and progression of PD.

• Authors: Mingmin Yan, Min Xiong, Lijun Dai, Xingyu Zhang, Yunhong Zha, Xiaorong Deng, Zhui Yu, Zhentao Zhang
• Journal: NPJ Parkinson's disease (NPJ Parkinsons Dis) Vol. 8 Issue 1 Pg. 1 (Jan 10 2022) ISSN: 2373-8057 [Print] United States
• PMID: 35013321 (Publication Type: Journal Article)
• Copyright: © 2022. The Author(s).