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The interaction of dopamine (DA) and α-synuclein (α-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 α-S aggregation under various solution conditions (i.e., pH, ionic strength) were investigated in vitro. The electrochemical oxidation of tyrosine (Tyr) residues in α-S was detected in the presence of DA. DA concentration dependence was analyzed and found to significantly affect α-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 α-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 α-S. Our results demonstrate the importance of solution interactions with α-S and the unique information that electrochemical techniques can provide for the investigation of α-S aggregation at early stages, an important step toward the development of future PD therapeutics.

The amyloid-b (Ab) aggregation pathway is an important target for the discovery of drugs that can prevent or delay the onset of Alzheimers disease (AD). The electrochemistry of Congo Red (CR) represents a particularly promising tool for screening of Ab-binding therapeutics in a rapid and cost-effective format. The results of the differential pulse voltammetry (DPV) measurements were confirmed using simultaneous UV-vis analysis of the same incubated Ab samples. The early changes in the electrochemical signals were attributed to the interaction of the Ab oligomers with CR. The electrochemical approach, in principle, allowed monitoring small molecule-Ab interactions on the time scale of aggregation.

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