The Early Events of α-Synuclein Oligomerization Revealed by Photo- Induced Cross-Linking

Assembly of α-synuclein (α-Syn) into neurotoxic oligomers and fibrils is an important pathogenic feature of Parkinson's disease. Studying the early events of α-Syn aggregation, such as oligomerization and nucleation, is indispensable to understanding the complicated process. Here, photo-induced cross-linking of unmodified proteins (PICUP) technique is applied to elucidate the early-stage oligomerization of α-Syn. Results show that α-Syn in solution exhibits a mixture of various species, including at least monomers, dimers and trimers. Aggregation of α-Syn probably originates from the dimeric and trimeric seeds. Furthermore, the N-terminal amphipathic region is proposed to be required for the oligomerization (dimerization and trimerization) process. This observation may extend our knowledge on the early events of α-Syn aggregation and the neurotoxic aggregation species.