Panicker Nikhil, Dawson Valina L, Dawson Ted M
Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, U.S.A.
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, U.S.A.
Biochem J. 2017 Aug 30;474(18):3075-3086. doi: 10.1042/BCJ20170476.
Monogenetic, familial forms of Parkinson's disease (PD) only account for 5-10% of the total number of PD cases, but analysis of the genes involved therein is invaluable to understanding PD-associated neurodegenerative signaling. One such gene, , encodes a 465 amino acid E3 ubiquitin ligase. Of late, there has been considerable interest in the role of parkin signaling in PD and in identifying its putative substrates, as well as the elucidation of the mechanisms through which parkin itself is activated. Its dysfunction underlies both inherited and idiopathic PD-associated neurodegeneration. Here, we review recent literature that provides a model of activation of parkin in the setting of mitochondrial damage that involves PINK1 (PTEN-induced kinase-1) and phosphoubiquitin. We note that neuronal parkin is primarily a cytosolic protein (with various non-mitochondrial functions), and discuss potential cytosolic parkin activation mechanisms.
帕金森病（PD）的单基因、家族性形式仅占PD病例总数的5-10%，但对其中涉及的基因进行分析对于理解与PD相关的神经退行性信号传导具有重要价值。其中一个这样的基因编码一种465个氨基酸的E3泛素连接酶。最近，人们对帕金森蛋白信号在PD中的作用、确定其假定底物以及阐明帕金森蛋白自身被激活的机制产生了浓厚兴趣。其功能障碍是遗传性和特发性PD相关神经退行性变的基础。在这里，我们回顾了最近的文献，这些文献提供了一种在涉及PINK1（PTEN诱导激酶-1）和磷酸泛素的线粒体损伤情况下激活帕金森蛋白的模型。我们注意到神经元帕金森蛋白主要是一种胞质蛋白（具有各种非线粒体功能），并讨论了潜在的胞质帕金森蛋白激活机制。
