Department of Pathology and Laboratory Medicine, Institute on Aging and Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, PA, 19104, USA.
Lab Invest. 2019 Jul;99(7):971-981. doi: 10.1038/s41374-019-0195-z. Epub 2019 Feb 13.
Cell-to-cell transmission of proteopathic alpha-synuclein (α-syn) seeds is increasingly thought to underlie the progression of neurodegenerative diseases including Parkinson's disease, dementia with Lewy bodies, multiple system atrophy, and related synucleinopathies. As such, it is important to understand the chemical and biological relationships between cells and pathological aggregates of α-syn. This brief review updates our understanding of the templated spread of α-syn pathology in neurodegenerative disease from the perspective of proteopathic α-syn seeds, including how these seeds are processed by cells as well as their effects on cellular function. Recent advances in understanding the conformations of α-syn seeds are highlighted, and the possible structural basis for the observed heterogeneity of synucleinopathies is discussed. Finally, we propose the possibility that some known risk factors for synucleinopathies may in fact potentiate the cell-to-cell transmission of α-syn pathology via imbalances in interrelated cell biological processes.
细胞间传播的朊病毒样α-突触核蛋白（α-syn）种子被认为是包括帕金森病、路易体痴呆、多系统萎缩和相关突触核蛋白病在内的神经退行性疾病进展的基础。因此，了解细胞与α-syn 病理性聚集物之间的化学和生物学关系非常重要。这篇简短的综述从朊病毒样α-syn 种子的角度更新了我们对神经退行性疾病中 α-syn 病理学模板传播的理解，包括这些种子如何被细胞加工以及它们对细胞功能的影响。强调了最近在理解 α-syn 种子构象方面的进展，并讨论了观察到的突触核蛋白病异质性的可能结构基础。最后，我们提出了这样一种可能性，即一些已知的突触核蛋白病风险因素实际上可能通过相关细胞生物学过程的不平衡促进 α-syn 病理学的细胞间传播。
