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

Abstract

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.

• Authors: Mingmin Yan, Lanxia Meng, Lijun Dai, Xingyu Zhang, Guiqin Chen, Yongfa Zheng, Yunhong Zha, Yan Zeng, Zhentao Zhang
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 529 Issue 4 Pg. 1053-1060 (09 03 2020) ISSN: 1090-2104 [Electronic] United States
• PMID: 32819564 (Publication Type: Journal Article)
• Copyright: Copyright © 2020 Elsevier Inc. All rights reserved.

Chemical References

• Cofilin 1
• Protein Aggregates
• alpha-Synuclein

Topics

• Animals
• Brain (metabolism, pathology)
• Cofilin 1 (metabolism)
• HEK293 Cells
• Humans
• Mice, Transgenic
• Parkinson Disease (metabolism)
• Protein Aggregates
• Protein Binding
• alpha-Synuclein (metabolism, toxicity)