Department of Physiology, Anatomy and Genetics, Oxford Parkinson's Disease Centre, University of Oxford, South Parks Road, Oxford, OX1 3QT, UK.
Montreal Neurological Institute, McGill University, 3801 Rue University, Montreal, QC, H3A 2B4, Canada.
Acta Neuropathol. 2017 Dec;134(6):819-838. doi: 10.1007/s00401-017-1755-1. Epub 2017 Aug 12.
Alpha-synuclein is a protein implicated in Parkinson's disease and thought to be one of the main pathological drivers in the disease, although it remains unclear how this protein elicits its neurotoxic effects. Recent findings indicate that the assembly of toxic oligomeric species of alpha-synuclein may be one of the key processes for the pathology and spread of the disease. The absence of a sensitive in situ detection method has hindered the study of these oligomeric species and the role they play in the human brain until recently. In this review, we assess the evidence for the toxicity and prion-like activity of oligomeric forms of alpha-synuclein and discuss the advances in our understanding of the role of alpha-synuclein in Parkinson's disease that may be brought about by the specific and sensitive detection of distinct oligomeric species in post-mortem patient brain. Finally, we discuss current approaches being taken to therapeutically target alpha-synuclein oligomers and their implications.
α-突触核蛋白是一种与帕金森病相关的蛋白，被认为是该疾病的主要病理驱动因素之一，尽管其如何引发神经毒性作用仍不清楚。最近的研究结果表明，α-突触核蛋白的毒性寡聚体的组装可能是该疾病的病理学和传播的关键过程之一。直到最近，缺乏敏感的原位检测方法一直阻碍了对这些寡聚体及其在人脑中的作用的研究。在这篇综述中，我们评估了α-突触核蛋白寡聚体的毒性和朊病毒样活性的证据，并讨论了通过在尸检患者大脑中特异性和敏感地检测不同的寡聚体，我们对α-突触核蛋白在帕金森病中的作用的理解可能取得的进展。最后，我们讨论了目前针对α-突触核蛋白寡聚体的治疗靶点及其影响的方法。
