Interactions of α-synuclein oligomers with lipid membranes

Abstract

Parkinson's disease is an increasingly prevalent and currently incurable neurodegenerative disorder. At the molecular level, this disease is characterized by the formation of aberrant intracellular protein deposits known as Lewy bodies. Oligomeric forms of the protein α-synuclein (αS), which are believed to be both intermediates and by-products of Lewy body formation, are considered to be the main pathogenic species. Interactions of such oligomers with lipid membranes are increasingly emerging as a major molecular pathway underpinning their toxicity. Here we review recent progress in our understanding of the interactions of αS oligomers with lipid membranes. We highlight key structural and biophysical features of αS oligomers, the effects of these features on αS oligomer membrane binding properties, and resultant implications for understanding the etiology of Parkinson's disease. We discuss mechanistic modes of αS oligomer-lipid membrane interactions and the effects of environmental factors to such modes. Finally, we provide an overview of the current understanding of the main molecular determinants of αS oligomer toxicity in vivo.

Keywords: Aggregation; Alpha-synuclein; Lipids; Membranes; Oligomers; Parkinson's disease.