Ebanks Kirsten, Lewis Patrick A, Bandopadhyay Rina
Reta Lila Weston Institute, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom.
Department of Clinical and Motor Neuroscience, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom.
Front Neurosci. 2020 Jan 8;13:1381. doi: 10.3389/fnins.2019.01381. eCollection 2019.
Parkinson's disease (PD) is a common age-related neurodegenerative disorder with disabling motor symptoms and no available disease modifying treatment. The majority of the PD cases are of unknown etiology, with both genetics and environment playing important roles. Over the past 25 years, however, genetic analysis of patients with familial history of Parkinson's and, latterly, genome wide association studies (GWAS) have provided significant advances in our understanding of the causes of the disease. These genetic insights have uncovered pathways that are affected in both genetic and sporadic forms of PD. These pathways involve oxidative stress, abnormal protein homeostasis, mitochondrial dysfunction, and lysosomal defects. In addition, newly identified PD genes and GWAS nominated genes point toward synaptic changes involving vesicles. This review will highlight the genes that contribute PD risk relating to intracellular vesicle trafficking and their functional consequences. There is still much to investigate on this newly identified and converging pathway of vesicular dynamics and PD, which will aid in better understanding and suggest novel therapeutic strategies for PD patients.
帕金森病（PD）是一种常见的与年龄相关的神经退行性疾病，具有致残性运动症状，且尚无有效的疾病修饰治疗方法。大多数帕金森病病例病因不明，遗传因素和环境因素都起着重要作用。然而，在过去25年里，对有帕金森病家族史患者的基因分析以及最近的全基因组关联研究（GWAS），在我们对该疾病病因的理解方面取得了重大进展。这些遗传学见解揭示了在帕金森病的遗传形式和散发性形式中均受影响的途径。这些途径涉及氧化应激、异常蛋白质稳态、线粒体功能障碍和溶酶体缺陷。此外，新发现的帕金森病基因和GWAS提名基因指向涉及囊泡的突触变化。本综述将重点介绍与细胞内囊泡运输相关的帕金森病风险基因及其功能后果。关于这个新发现的且相互关联的囊泡动力学与帕金森病途径，仍有许多有待研究的内容，这将有助于更好地理解并为帕金森病患者提出新的治疗策略。
