Disruptive membrane interactions of alpha-synuclein aggregates

Alpha synuclein (alpha S) is a similar to 14 kDa intrinsically disordered protein. Decades of research have increased our knowledge on alpha Syet its physiological function remains largely elusive. The conversion of monomeric alpha S into oligomers and amyloid fibrils is believed to play a central role of the pathology of Parkinson's disease (PD). It is becoming increasingly clear that the interactions of alpha S with cellular membranes are important for both alpha S's functional and pathogenic actions. Therefore, understanding interactions of alpha S with membranes seems critical to uncover functional or pathological mechanisms. This review summarizes our current knowledge of how physicochemical properties of phospholipid membranes affect the binding and aggregation of alpha S species and gives an overview of how post-translational modifications and point mutations in alpha S affect phospholipid membrane binding and protein aggregation. We discuss the disruptive effects resulting from the interaction of alpha S aggregate species with membranes and highlight current approaches and hypotheses that seek to understand the pathogenic and/or protective role of alpha S in PD.