The Membrane Interaction of Alpha-Synuclein

A presynaptic protein closely related to Parkinson's disease (PD), alpha-synuclein (alpha-Syn), has been studied extensively regarding its pathogenic mechanisms. As a physiological protein in presynapses, however, alpha-Syn's physiological function remains unclear. Its location in nerve terminals and effects on membrane fusion also imply its functional role in synaptic transmission, including its possible interaction with high-curvature membranes via its N-terminus and amorphous C-terminus. PD-related mutants that disrupt the membrane interaction (e.g., A30P and G51D) additionally suggest a relationship between alpha-Syn's pathogenic mechanisms and physiological roles through the membrane binding. Here, we summarize recent research on how alpha-Syn and its variants interact with membranes and influence synaptic transmission. We list several membrane-related connections between the protein's physiological function and the pathological mechanisms that stand to expand current understandings of alpha-Syn.