Membrane binding of oligomeric alpha-synuclein depends on bilayer charge and packing

FEBS Lett. 2008 Nov 12;582(27):3788-92. doi: 10.1016/j.febslet.2008.10.009. Epub 2008 Oct 16.


Membrane disruption by oligomeric alpha-synuclein (alphaS) is considered a likely mechanism of cytotoxicity in Parkinson's disease (PD). However, the mechanism of oligomer binding and the relation between binding and membrane disruption is not known. We have visualized alphaS oligomer-lipid binding by fluorescence microscopy and have measured membrane disruption using a dye release assay. The data reveal that oligomeric alphaS selectively binds to membranes containing anionic lipids and preferentially accumulates into liquid disordered (Ld) domains. Furthermore, we show that binding of oligomers to the membrane and disruption of the membrane require different lipid properties. Thus membrane-bound oligomeric alphaS does not always cause bilayer disruption.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Lipid Bilayers / chemistry
  • Lipid Bilayers / metabolism*
  • Microscopy, Confocal
  • Microscopy, Fluorescence
  • Parkinson Disease / metabolism
  • Permeability
  • alpha-Synuclein / chemistry
  • alpha-Synuclein / metabolism*


  • Lipid Bilayers
  • alpha-Synuclein