Oxidative Stress Effect of Dopamine on α-Synuclein: Electroanalysis of Solvent Interactions

The interaction of dopamine (DA) and alpha-synuclein (alpha-S) can lead to protein misfolding and neuronal death triggered by oxidative stress relevant to the progression of Parkinson's disease (PD). In this study, interfacial properties associated with DA-induced alpha-S aggregation under various solution conditions (i.e., pH, ionic strength) were investigated in vitro. The electrochemical oxidation of tyrosine (Tyr) residues in alpha-S was detected in the presence of DA. DA concentration dependence was analyzed and found to significantly affect alpha-S aggregation pathways. At low pH, DA was shown to be stable and produced no observable difference in interfacial properties. Between pH 7 and 11, DA promoted alpha-S aggregation. Significant differences in oxidation current signals in response to high pH and ionic strength suggested the importance of initial interactions in the stabilization of toxic oligomeric structures and subsequent off-pathways of alpha-S. Our results demonstrate the importance of solution interactions with alpha-S and the unique information that electrochemical techniques can provide for the investigation of alpha-S aggregation at early stages, an important step toward the development of future PD therapeutics.