Exploring the accessible conformations of N-terminal acetylated α-synuclein

Alpha synuclein (alpha syn) fibrils are found in the Lewy Bodies of patients with Parkinson's disease (PD). The aggregation of the alpha syn monomer to soluble oligomers and insoluble fibril aggregates is believed to be one of the causes of PD. Recently, the view of the native state of alpha syn as a monomeric ensemble was challenged by a report suggesting that alpha syn exists in its native state as a helical tetramer. This review reports on our current understanding of alpha syn within the context of these recent developments and describes the work performed by a number of groups to address the monomer/tetramer debate. A number of in depth studies have subsequently shown that both non-acetylated and acetylated alpha syn purified under mild conditions are primarily monomer. A description of the accessible states of acetylated alpha syn monomer and the ability of alpha syn to self-associate is explored. (C) 2013 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.