Oligomeric α-synuclein inhibits tubulin polymerization

Abstract

Earlier investigations have demonstrated that tubulin co-localizes with α-synuclein in Lewy bodies and influences the formation of α-synuclein aggregation. However, it is not clear whether aggregated α-synuclein has any effects on the function of tubulin, i.e. tubulin polymerization, a critical mechanism by which neurons maintain their morphology and execute functions. In this study, we evaluated the effects of aggregated α-synuclein on tubulin polymerization in dopaminergic neurons (MES cells), along with mitochondrial function, cell morphology, and viability. The results indicate that MES cells exposed to extracellular oligomeric α-synuclein exhibited decreased tubulin polymerization and mitochondrial function as well as morphological alternation long before cell death. Further investigation showed that internalization of oligomeric α-synuclein by neurons appeared to be critical in the process, although direct interaction between tubulin and intracellular oligomeric α-synuclein was not necessary. Finally, we demonstrated that neurotoxicity induced by oligomeric α-synuclein was largely prevented by overexpressing the neuroprotective protein, DJ-1.