Amyloid formation is a pathological hallmark of many neurodegenerative diseases, including Alzheimer's, Parkinson's, and Huntington's. While it is unknown how these disorders are initiated, in vitro and cellular experiments confirm the importance of membranes. Ubiquitous in vivo, membranes induce conformational changes in amyloidogenic proteins and in some cases, facilitate aggregation. Reciprocally, perturbations in the bilayer structure can be induced by amyloid formation. Here, we review studies in the last 10 years describing α-synuclein (α-syn) and its interactions with membranes, detailing the roles of anionic and zwitterionic lipids in aggregation, and their contribution to Parkinson's disease. We summarize the impact of α-syn - comparing monomeric, oligomeric, and fibrillar forms - on membrane structure, and the effect of membrane remodeling on amyloid formation. Finally, perspective on future studies investigating the interplay between α-syn aggregation and membranes is discussed. This article is part of a Special Issue entitled: Amyloids.
Keywords: Aggregation; Membrane remodeling; Parkinson's disease; Protein-lipid interaction; Thioflavin T; Tubulation.
Published by Elsevier B.V.