First Author | Feng LR | Year | 2010 |
Journal | Eur J Neurosci | Volume | 32 |
Issue | 1 | Pages | 10-7 |
PubMed ID | 20550572 | Mgi Jnum | J:171788 |
Mgi Id | MGI:4999704 | Doi | 10.1111/j.1460-9568.2010.07266.x |
Citation | Feng LR, et al. (2010) Alpha-synuclein mediates alterations in membrane conductance: a potential role for alpha-synuclein oligomers in cell vulnerability. Eur J Neurosci 32(1):10-7 |
abstractText | 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. |