Cofilin 1 promotes the aggregation and cell-to-cell transmission of α-synuclein in Parkinson's disease.

Mingmin Yan, Lanxia Meng, Lijun Dai, Xingyu Zhang, Guiqin Chen, Yongfa Zheng, Yunhong Zha, Yan Zeng, Zhentao Zhang

Biochemical and biophysical research communications 2020 Sep 03

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The histopathological hallmark of Parkinson's disease (PD) is the presence of fibrillar aggregates referred to as Lewy bodies (LBs), in which α-synuclein is the major component. Converging evidence supports the prion-like transmission of α-synuclein aggregates in the onset and progression of PD. Intracellular α-synuclein aggregates into pathological fibrils, which can be transferred from aggregate-producing cells to aggregate-free cells, triggering neuronal injury and the progression of pathology. However, the specific mechanisms mediating the aggregation and transmission of pathological α-synuclein remain unknown. Here we show that cofilin 1 binds to α-synuclein and promotes its aggregation. The mixed fibrils consist of cofilin 1 and α-synuclein are more compact and more potent than pure α-synuclein fibrils in seeding α-synuclein aggregation. Cofilin 1 also facilitates the uptake of α-synuclein fibrils and finally induces neuronal dysfunction. Together, these observations indicate that cofilin 1 acts as a crucial mediator in the aggregation and propagation of pathological α-synuclein, contributing to the pathogenesis of PD. Copyright © 2020 Elsevier Inc. All rights reserved.

Citation

Mingmin Yan, Lanxia Meng, Lijun Dai, Xingyu Zhang, Guiqin Chen, Yongfa Zheng, Yunhong Zha, Yan Zeng, Zhentao Zhang. Cofilin 1 promotes the aggregation and cell-to-cell transmission of α-synuclein in Parkinson's disease. Biochemical and biophysical research communications. 2020 Sep 03;529(4):1053-1060