Laboratory of Molecular and Chemical Biology of Neurodegeneration, Brain Mind Institute, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland.
Nat Rev Neurosci. 2013 Jan;14(1):38-48. doi: 10.1038/nrn3406.
Disorders characterized by α-synuclein (α-syn) accumulation, Lewy body formation and parkinsonism (and in some cases dementia) are collectively known as Lewy body diseases. The molecular mechanism (or mechanisms) through which α-syn abnormally accumulates and contributes to neurodegeneration in these disorders remains unknown. Here, we provide an overview of current knowledge and prevailing hypotheses regarding the conformational, oligomerization and aggregation states of α-syn and their role in regulating α-syn function in health and disease. Understanding the nature of the various α-syn structures, how they are formed and their relative contributions to α-syn-mediated toxicity may inform future studies aiming to develop therapeutic prevention and intervention.
以 α-突触核蛋白（α-syn）积累、路易体形成和帕金森病（在某些情况下还有痴呆）为特征的疾病统称为路易体疾病。导致这些疾病中 α-syn 异常积累并导致神经退行性变的分子机制（或多种机制）仍不清楚。在这里，我们提供了关于 α-syn 的构象、寡聚体和聚集状态及其在调节健康和疾病中 α-syn 功能方面的当前知识和主流假说的概述。了解各种 α-syn 结构的性质、它们是如何形成的以及它们对 α-syn 介导的毒性的相对贡献，可能为旨在开发治疗预防和干预措施的未来研究提供信息。
