Appel Institute for Alzheimer's Disease Research, Brain and Mind Research Institute, Weill Cornell Medicine, New York, New York 10021.
Departments of Molecular and Cellular Physiology, Stanford University Medical School, Stanford, California 94305.
Cold Spring Harb Perspect Med. 2018 Mar 1;8(3):a024091. doi: 10.1101/cshperspect.a024091.
α-Synuclein is an abundant neuronal protein that is highly enriched in presynaptic nerve terminals. Genetics and neuropathology studies link α-synuclein to Parkinson's disease (PD) and other neurodegenerative disorders. Accumulation of misfolded oligomers and larger aggregates of α-synuclein defines multiple neurodegenerative diseases called synucleinopathies, but the mechanisms by which α-synuclein acts in neurodegeneration are unknown. Moreover, the normal cellular function of α-synuclein remains debated. In this perspective, we review the structural characteristics of α-synuclein, its developmental expression pattern, its cellular and subcellular localization, and its function in neurons. We also discuss recent progress on secretion of α-synuclein, which may contribute to its interneuronal spread in a prion-like fashion, and describe the neurotoxic effects of α-synuclein that are thought to be responsible for its role in neurodegeneration.
α-突触核蛋白是一种丰富的神经元蛋白，在突触前神经末梢中高度富集。遗传学和神经病理学研究将 α-突触核蛋白与帕金森病 (PD) 和其他神经退行性疾病联系起来。错误折叠的寡聚物和更大的 α-突触核蛋白聚集体的积累定义了多种称为突触核蛋白病的神经退行性疾病，但 α-突触核蛋白在神经退行性变中的作用机制尚不清楚。此外，α-突触核蛋白的正常细胞功能仍存在争议。在这篇观点文章中，我们回顾了 α-突触核蛋白的结构特征、其发育表达模式、细胞和亚细胞定位以及其在神经元中的功能。我们还讨论了 α-突触核蛋白分泌的最新进展，这可能有助于其以类朊病毒的方式在神经元间传播，并描述了被认为是其在神经退行性变中作用的原因的 α-突触核蛋白的神经毒性作用。
