Deletion in exon 5 of the SNCA gene and exposure to rotenone leads to oligomerization of α-synuclein and toxicity to PC12 cells

Abstract

α-Synuclein (α-syn) is a presynaptic protein that is widely implicated in the pathophysiology of Parkinson's disease (PD). Recently, four α-syn isoforms that are produced by alternative splicing have been described, they are α-syn140, α-syn126, α-syn112, and α-syn98. The stable cell lines which expressed the four α-syn isoforms respectively were obtained, and the aggregation formation of these α-syn isoforms and their associated toxicity to PC12 cell were investigated. The results of this study indicate that over-expression of α-syn isoforms alone in dopaminergic cells have no effect on the formation of α-syn oligomeric species and cell viabilities. When exposed to rotenone, these cell lines which over expressed exon 5-lacking form of α-syn isoforms showed the formation of oligomeric species and toxicity to PC12 cells.