Alpha-synuclein (αS) is the major constituent of Lewy bodies and a pathogenic hallmark of all synucleinopathathies, including Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). All diseases are determined by αS aggregate deposition but can be separated into distinct pathological phenotypes and diagnostic criteria. Here we attempt to reinterpret the literature, particularly in terms of how αS structure may relate to pathology. We do so in the context of a rapidly evolving field, taking into account newly revealed structural information on both native and pathogenic forms of the αS protein, including recent solid state NMR and cryoEM fibril structures. We discuss how these new findings impact on current understanding of αS and PD, and where this information may direct the field.

中文翻译：

---

α-突触核蛋白结构和帕金森病 - 经验教训和新出现的原则。


α-突触核蛋白 (αS) 是路易体的主要成分，也是所有突触核蛋白病的致病标志，包括帕金森病 (PD)、路易体痴呆 (DLB) 和多系统萎缩 (MSA)。所有疾病均由 αS 聚集体沉积决定，但可分为不同的病理表型和诊断标准。在这里，我们尝试重新解释文献，特别是在 αS 结构与病理学的关系方面。我们在一个快速发展的领域的背景下这样做，考虑到新发现的 αS 蛋白天然和致病形式的结构信息，包括最近的固态 NMR 和冷冻电镜原纤维结构。我们讨论这些新发现如何影响当前对 αS 和 PD 的理解，以及这些信息可能指导该领域的方向。