Mechanistic aspects of Parkinson's disease: alpha-synuclein and the biomembrane

Abstract

AA key feature in Parkinson's disease is the deposition of Lewy bodies. The major protein component of these intracellular deposits is the 140-amino acid protein alpha-synuclein that is widely distributed throughout the brain. alpha-synuclein was identified in presynaptic terminals and in synaptosomal preparations. The protein is remarkable for its structural variability. It is almost unstructured as a monomer in aqueous solution. Self-aggregation leads to a variety of beta-structures, while membrane association may result in the formation of an amphipathic helical structure. The present article strives to give an overview of what is currently known on the interaction of alpha-synuclein with lipid membranes, including synthetic lipid bilayers, membraneous cell fractions, synaptic vesicles and intact cells. Manifestations of a functional relevance of the alpha-synuclein-lipid interaction will be discussed and the potential pathogenicity of oligomeric alpha-synuclein aggregates will be briefly reviewed.