Tokyo Metropolitan Institute of Medical Science, Japan.
Neurosci Res. 2020 Oct;159:9-15. doi: 10.1016/j.neures.2020.01.006. Epub 2020 Jan 23.
Parkin is a protein involved in familial Parkinson's disease (PD), a neurodegenerative disorder with motor symptoms linked to the loss of dopaminergic neurons. More than 20 years have passed since the discovery of Parkin; since that time, another familial PD protein has been identified: PINK1, which acts upstream of Parkin. PINK1 is a protein kinase that monitors mitochondrial integrity by sensing disability status, whereas Parkin is a ubiquitin-protein ligase that attaches ubiquitin chains to malfunctioning mitochondria as a degradation signal. Both enzymes cooperatively facilitate autophagic clearance of damaged mitochondria (also known as mitophagy). Collectively, the PINK1-Parkin axis functions as the core machinery for mitophagy in neurons, and deficiency in this pathway causes early-onset PD. In this review, I will discuss how the PINK1-Parkin study has progressed, with the personal episodes I have experienced.
帕金蛋白参与家族性帕金森病（PD），这是一种神经退行性疾病，运动症状与多巴胺能神经元的丧失有关。自帕金蛋白发现以来已经过去了 20 多年；自那时以来，又发现了另一种家族性 PD 蛋白：PINK1，它位于帕金蛋白的上游。PINK1 是一种蛋白激酶，通过感应失能状态来监测线粒体的完整性，而帕金蛋白是一种泛素蛋白连接酶，它将泛素链连接到功能失调的线粒体上作为降解信号。这两种酶协同促进受损线粒体的自噬清除（也称为线粒体自噬）。PINK1-Parkin 轴共同作为神经元中线粒体自噬的核心机制，该途径的缺陷会导致早发性 PD。在这篇综述中，我将讨论我个人经历的 PINK1-Parkin 研究进展。
