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Cofilin 1 promotes the aggregation and cell-to-cell transmission of α-synuclein in Parkinson's disease.
- Source :
-
Biochemical & Biophysical Research Communications . Sep2020, Vol. 529 Issue 4, p1053-1060. 8p. - Publication Year :
- 2020
-
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. • Cofilin 1 was highly expressed in human and mouse PD brains. • Cofilin 1 combined α-synuclein and promoted its aggregation. • Cofilin 1 facilitated the propagation of α-synuclein pathology. • Cofilin 1 enhanced the toxicity of α-synuclein fibrils. [ABSTRACT FROM AUTHOR]
- Subjects :
- *PARKINSON'S disease
*PATHOLOGY
Subjects
Details
- Language :
- English
- ISSN :
- 0006291X
- Volume :
- 529
- Issue :
- 4
- Database :
- Academic Search Index
- Journal :
- Biochemical & Biophysical Research Communications
- Publication Type :
- Academic Journal
- Accession number :
- 145203191
- Full Text :
- https://doi.org/10.1016/j.bbrc.2020.06.101