Department of Biological Sciences, Boise State University, Boise, ID 83725, USA; Biomolecular Sciences Ph.D. Program, Boise State University, Boise, ID 83725, USA.
Department of Biological Sciences, Boise State University, Boise, ID 83725, USA; Biomolecular Sciences Ph.D. Program, Boise State University, Boise, ID 83725, USA.
Neuroscience. 2019 Mar 1;401:1-10. doi: 10.1016/j.neuroscience.2019.01.006. Epub 2019 Jan 18.
Parkinson's Disease (PD) is a multi-system neurodegenerative disease where approximately 90% of cases are idiopathic. The remaining 10% of the cases can be traced to a genetic origin and research has largely focused on these associated genes to gain a better understanding of the molecular and cellular pathogenesis for PD. The gene encoding vacuolar protein sorting protein 35 (VPS35) has been definitively linked to late onset familial PD following the identification of a point mutation (D620N) as the causal agent in a Swiss family. Since its discovery, numerous studies have been undertaken to characterize the role of VPS35 in cellular processes and efforts have been directed toward understanding the perturbations caused by the D620N mutation. In this review, we examine what is currently known about VPS35, which has pleiotropic effects, as well as proposed mechanisms of pathogenesis by the D620N mutation. A brief survey of other VPS35 polymorphisms is also provided. Lastly, model systems that are being utilized for these investigations and possible directions for future research are discussed.
帕金森病（PD）是一种多系统神经退行性疾病，约 90%的病例为特发性。其余 10%的病例可以追溯到遗传起源，研究主要集中在这些相关基因上，以更好地了解 PD 的分子和细胞发病机制。编码液泡蛋白分选蛋白 35（VPS35）的基因与晚发性家族性 PD 明确相关，此前在一个瑞士家族中发现了一个点突变（D620N）作为致病因子。自发现以来，已经进行了许多研究来描述 VPS35 在细胞过程中的作用，并努力理解 D620N 突变引起的干扰。在这篇综述中，我们检查了目前已知的 VPS35，它具有多效性作用，以及 D620N 突变引起的发病机制的建议机制。还简要调查了其他 VPS35 多态性。最后，讨论了用于这些研究的模型系统和未来研究的可能方向。
