Polycation‐induced oligomerization and accelerated fibrillation of human α‐synuclein in vitro

The aggregation and fibrillation of α‐synuclein has been implicated as a causative factor in Parkinson's disease and several other neurodegenerative disorders known as synucleinopathies. The effect of different factors on the process of fibril formation has been intensively studied in vitro. We show here that α‐synuclein interacts with different unstructured polycations (spermine, polylysine, polyarginine, and polyethyleneimine) to form specific complexes. In addition, the polycations catalyze α‐synuclein oligomerization. The formation of α‐synuclein–polycation complexes was not accompanied by significant structural changes in α‐synuclein. However, α‐synuclein fibrillation was dramatically accelerated in the presence of polycations. The magnitude of the accelerating effect depended on the nature of the polymer, its length, and concentration. The results illustrate the potential critical role of electrostatic interactions in protein aggregation, and the potential role of naturally occurring polycations in modulating α‐synuclein aggregation.