Sheehan Patricia, Yue Zhenyu
Department of Neurology, The Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, 10029, USA.
Department of Neurology, The Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, 10029, USA.
Neurosci Lett. 2019 Apr 1;697:59-65. doi: 10.1016/j.neulet.2018.04.013. Epub 2018 Apr 5.
Parkinson's disease (PD) is a common neurodegenerative disease characterized pathologically by the selective loss of dopaminergic neurons in the substantia nigra and the intracellular accumulation of α-synuclein in the Lewy bodies. While the pathogenic mechanisms of PD are poorly understood, many lines of evidence point to a role of altered autophagy and membrane trafficking in the development of the disease. Emerging studies show that connections between the deregulation of autophagy and synaptic vesicle (SV) trafficking may contribute to PD. Here we review the evidence that many PD related-genes have roles in both autophagy and SV trafficking and examine how deregulation of these pathways contributes to PD pathogenesis. This review also discusses recent studies aimed at uncovering the role of PD-linked genes in autophagy-lysosome function.
帕金森病(PD)是一种常见的神经退行性疾病,其病理特征是黑质中多巴胺能神经元选择性丧失以及路易小体中α-突触核蛋白的细胞内积聚。虽然PD的致病机制尚不清楚,但许多证据表明自噬和膜运输改变在该疾病的发展中起作用。新兴研究表明,自噬失调与突触小泡(SV)运输之间的联系可能与PD有关。在此,我们综述了许多与PD相关的基因在自噬和SV运输中均起作用的证据,并探讨了这些途径的失调如何导致PD发病机制。本综述还讨论了旨在揭示与PD相关基因在自噬-溶酶体功能中的作用的近期研究。