Hunn Benjamin H M, Cragg Stephanie J, Bolam J Paul, Spillantini Maria-Grazia, Wade-Martins Richard
Oxford Parkinson's Disease Centre, University of Oxford, South Parks Road, Oxford OX1 3QX, UK; Department of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford OX1 3QX, UK.
Oxford Parkinson's Disease Centre, University of Oxford, South Parks Road, Oxford OX1 3QX, UK; Medical Research Council Anatomical Neuropharmacology Unit, Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3QT, UK.
Trends Neurosci. 2015 Mar;38(3):178-88. doi: 10.1016/j.tins.2014.12.009. Epub 2015 Jan 29.
Parkinson's disease (PD) is an insidious and incurable neurodegenerative disease, and represents a significant cost to individuals, carers, and ageing societies. It is defined at post-mortem by the loss of dopamine neurons in the substantia nigra together with the presence of Lewy bodies and Lewy neurites. We examine here the role of α-synuclein and other cellular transport proteins implicated in PD and how their aberrant activity may be compounded by the unique anatomy of the dopaminergic neuron. This review uses multiple lines of evidence from genetic studies, human tissue, induced pluripotent stem cells, and refined animal models to argue that prodromal PD can be defined as a disease of impaired intracellular trafficking. Dysfunction of the dopaminergic synapse heralds trafficking impairment.
帕金森病（PD）是一种隐匿且无法治愈的神经退行性疾病，给患者个人、照料者以及老龄化社会带来了巨大的负担。尸检时，帕金森病的定义为黑质中多巴胺能神经元的丧失以及路易小体和路易神经突的存在。我们在此探讨α-突触核蛋白和其他与帕金森病相关的细胞转运蛋白的作用，以及多巴胺能神经元独特的解剖结构如何加剧它们的异常活动。本综述综合了来自基因研究、人体组织、诱导多能干细胞和改良动物模型的多条证据，认为帕金森病前驱期可被定义为一种细胞内运输受损的疾病。多巴胺能突触功能障碍预示着运输功能受损。
