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.