Tuning the Balance between Fibrillation and Oligomerization of α-Synuclein in the Presence of Dopamine

ACS Omega. 2018 Oct 31;3(10):14213-14224. doi: 10.1021/acsomega.8b00993. Epub 2018 Oct 26.

Abstract

The aggregates of α-synuclein bear a close connection with Parkinson's disease, which is largely characterized by the loss of the dopaminergic neurons. Dopamine promotes the formation of undesirable sodium dodecyl sulfate (SDS)-resistant oligomers of α-synuclein. In this study, we have shown that the inhibition of fibrillation by an additive may not always be the ultimate deciding factor in the context of its potential as a successful additive. Copper promotes the fibrillation of α-synuclein in buffer alone but inhibits the formation of SDS-resistant oligomers in the presence of dopamine. Glycerol, on the other hand, increases the population of such dopamine-mediated SDS-resistant oligomers. We speculate such an effect to be a manifestation of the distinct oxidation pathway of dopamine in the presence of copper.