Barodia Sandeep K, Creed Rose B, Goldberg Matthew S
Center for Neurodegeneration and Experimental Therapeutics, Department of Neurology, The University of Alabama at Birmingham, Birmingham, AL 35294, United States.
Center for Neurodegeneration and Experimental Therapeutics, Department of Neurology, The University of Alabama at Birmingham, Birmingham, AL 35294, United States; Department of Neurobiology, The University of Alabama at Birmingham, Birmingham, AL 35294, United States.
Brain Res Bull. 2017 Jul;133:51-59. doi: 10.1016/j.brainresbull.2016.12.004. Epub 2016 Dec 23.
Loss-of-function mutations in the genes encoding Parkin and PINK1 are causally linked to autosomal recessive Parkinson's disease (PD). Parkin, an E3 ubiquitin ligase, and PINK1, a mitochondrial-targeted kinase, function together in a common pathway to remove dysfunctional mitochondria by autophagy. Presumably, deficiency for Parkin or PINK1 impairs mitochondrial autophagy and thereby increases oxidative stress due to the accumulation of dysfunctional mitochondria that release reactive oxygen species. Parkin and PINK1 likely have additional functions that may be relevant to the mechanisms by which mutations in these genes cause neurodegeneration, such as regulating inflammation, apoptosis, or dendritic morphogenesis. Here we briefly review what is known about functions of Parkin and PINK1 related to oxidative stress and neurodegeneration.
编码帕金蛋白（Parkin）和PTEN诱导激酶1（PINK1）的基因功能丧失突变与常染色体隐性帕金森病（PD）存在因果关系。帕金蛋白是一种E3泛素连接酶，PINK1是一种定位于线粒体的激酶，二者在一条共同途径中协同发挥作用，通过自噬清除功能失调的线粒体。据推测，帕金蛋白或PINK1的缺乏会损害线粒体自噬，从而由于释放活性氧的功能失调线粒体的积累而增加氧化应激。帕金蛋白和PINK1可能还具有其他功能，这些功能可能与这些基因中的突变导致神经退行性变的机制相关，比如调节炎症、细胞凋亡或树突形态发生。在此，我们简要综述一下目前已知的帕金蛋白和PINK1与氧化应激及神经退行性变相关的功能。
