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

Shivnetra Saha, Mohammad Ashhar Iqbal Khan, Deepak Mudhara and 1 more

ACS Omega · 2018

doi:10.1021/acsomega.8b00993 (opens in a new tab)

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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.

Abstract licence: CC BY-NC-ND

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