Oxidative stress effect of dopamine on α-synuclein: electroanalysis of solvent interactions

ACS Chem Neurosci. 2012 Jul 18;3(7):569-74. doi: 10.1021/cn300034t. Epub 2012 May 16.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Dopamine / chemistry*
  • Dopamine / metabolism
  • Dopamine / physiology*
  • Electrochemistry
  • Oxidative Stress / physiology*
  • Solvents / chemistry
  • Solvents / metabolism*
  • alpha-Synuclein / chemistry
  • alpha-Synuclein / metabolism*

Substances

  • Solvents
  • alpha-Synuclein
  • Dopamine