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.

帕金森氏病是一种越来越普遍的，目前无法治愈的神经退行性疾病。在分子水平上，该疾病的特征是形成异常的细胞内蛋白质沉积物，称为路易小体。α-突触核蛋白（αS）的低聚形式被认为是路易体形成的中间产物和副产物，被认为是主要的致病菌。这种低聚物与脂质膜的相互作用日益成为支撑其毒性的主要分子途径。在这里，我们回顾了我们对αS低聚物与脂质膜相互作用的了解的最新进展。我们重点介绍了αS低聚物的关键结构和生物物理特征，这些特征对αS低聚物膜结合特性的影响，以及对理解帕金森病病因的启示。我们讨论了αS低聚物-脂质膜相互作用的机理模式以及环境因素对该模式的影响。最后，我们概述了对αS低聚物毒性的主要分子决定因素的当前了解体内。