Krembil Research Institute, Toronto Western Hospital, University Health Network, Toronto, Canada.
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada.
Crit Rev Clin Lab Sci. 2020 Aug;57(5):291-307. doi: 10.1080/10408363.2019.1711359. Epub 2020 Mar 1.
Parkinson's disease (PD) is the most common neurodegenerative movement disorder and is characterized by the accumulation of α-synuclein (α-syn) into insoluble aggregates known as Lewy bodies and Lewy neurites in the brain. However, prior to the formation of these large aggregates, α-syn forms oligomers and small fibrils, which are believed to be the pathogenic species leading to the death of neurons in the substantia nigra in disease. The majority of aggregated α-syn is phosphorylated, and it is thought that this post-translational modification may be critical in disease pathogenesis. Thus, early detection of the toxic forms of α-syn may provide a window of opportunity for an intervention to halt or slow the progression of neurodegeneration in PD. Expression of α-syn is not restricted to the central nervous system and the protein can be found elsewhere, including bodily fluids and peripheral tissues. This review will examine current methods for detecting toxic forms of α-syn in accessible biospecimens and outline emerging techniques that may provide reliable identification of biomarkers for PD.
帕金森病（PD）是最常见的神经退行性运动障碍，其特征是脑内α-突触核蛋白（α-syn）积累成不溶性聚集体，称为路易体和路易神经原纤维。然而，在这些大聚集体形成之前，α-syn 形成寡聚体和小纤维，据信这些聚集体是导致疾病中黑质神经元死亡的致病物质。大多数聚集的α-syn 被磷酸化，人们认为这种翻译后修饰可能在疾病发病机制中起关键作用。因此，早期检测有毒形式的α-syn 可能为干预提供机会，以阻止或减缓 PD 中的神经退行性变进展。α-syn 的表达不仅限于中枢神经系统，该蛋白也可以在其他地方发现，包括体液和外周组织。本综述将检查目前在可及生物标本中检测有毒形式α-syn 的方法，并概述可能为 PD 提供可靠生物标志物识别的新兴技术。
