α-Synuclein mediates alterations in membrane conductance: a potential role for α-synuclein oligomers in cell vulnerability

Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20057, USA.
European Journal of Neuroscience (Impact Factor: 3.67). 07/2010; 32(1):10-7. DOI: 10.1111/j.1460-9568.2010.07266.x
Source: PubMed

ABSTRACT alpha-Synuclein has been linked to the pathogenesis of Parkinson's disease and other synucleinopathies through its propensity to form toxic oligomers. The exact mechanism for oligomeric synuclein-directed cell vulnerability has not been fully elucidated, but one hypothesis portends the formation of synuclein-containing pores within cell membranes leading to leak channel-mediated calcium influx and subsequent cell death. Here we demonstrate synuclein-induced formation of sodium dodecyl sulfate-stable oligomers, intracellular synuclein-positive aggregates, alterations in membrane conductance reminiscent of leak channels and subsequent cytotoxicity in a dopaminergic-like cell line. Furthermore we demonstrate that the synuclein-induced membrane conductance changes are blocked by direct extracellular application of an anti-synuclein antibody. The work presented here confirms that synuclein overexpression leads to membrane conductance changes and demonstrates for the first time through antibody-blocking studies that synuclein plays a direct role in the formation of leak channels.


Available from: Howard Federoff, May 30, 2015
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