The histopathological hallmark of Parkinson's disease (PD) is the presence of fibrillar aggregates referred to as Lewy bodies (LBs), in which alpha-synuclein is the major component. Converging evidence supports the prion-like transmission of alpha-synuclein aggregates in the onset and progression of PD. Intracellular asynuclein 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 alpha-synuclein remain unknown. Here we show that cofilin 1 binds to alpha-synuclein and promotes its aggregation. The mixed fibrils consist of cofilin 1 and alpha-synuclein are more compact and more potent than pure alpha-synuclein fibrils in seeding alpha-synuclein aggregation. Cofilin 1 also facilitates the uptake of alpha-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 a-synuclein, contributing to the pathogenesis of PD. (c) 2020 Elsevier Inc. All rights reserved.