title: Oxidative stress effect of dopamine on α-synuclein: electroanalysis of solvent interactions.
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.
authors.affiliation: Department of Physical and Environmental Sciences, Department of Biological Sciences, University of Toronto Scarborough, 1265 Military Trail, Toronto, ON, M1C 1A4 Canada.
authors.forename: Tiffiny
authors.initials: T
authors.lastname: Chan
authors.forename: Ari M
authors.initials: AM
authors.lastname: Chow
authors.forename: Xin R
authors.initials: XR
authors.lastname: Cheng
authors.forename: Derek W F
authors.initials: DW
authors.lastname: Tang
authors.forename: Ian R
authors.initials: IR
authors.lastname: Brown
authors.forename: Kagan
authors.initials: K
authors.lastname: Kerman
mesh_terms: D004298:Dopamine / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology*; D004563:Electrochemistry; D018384:Oxidative Stress / Q000502:physiology*; D012997:Solvents / Q000737:chemistry / Q000378:metabolism*; D051844:alpha-Synuclein / Q000737:chemistry / Q000378:metabolism*
chemical_list: D012997:Solvents; D051844:alpha-Synuclein; D004298:Dopamine