Twenty-five years have passed since the causative gene for familial Parkinson's disease (PD), Parkin (now PRKN), was identified in 1998; PRKN is the most common causative gene in young-onset PD. Parkin encodes a ubiquitin-protein ligase, and Parkin is involved in mitophagy, a type of macroautophagy, in concert with PTEN-induced kinase 1 (PINK1). Both gene products are also involved in mitochondrial quality control. Among the many genetic PD-causing genes discovered, discovering PRKN as a cause of juvenile-onset PD has significantly impacted other neurodegenerative disorders. This is because the involvement of proteolytic systems has been suggested as a common mechanism in neurodegenerative diseases in which inclusion body formation is observed. The discovery of the participation of PRKN in PD has brought attention to the involvement of the proteolytic system in neurodegenerative diseases. Our research group has successfully isolated and identified CHCHD2, which is involved in the mitochondrial electron transfer system, and prosaposin (PSAP), which is involved in the lysosomal system, in this Parkin mechanism. Hereditary PD is undoubtedly an essential clue to solitary PD, and at least 25 or so genes and loci have been reported so far. This number of genes indicates that PD is a very diverse group of diseases. Currently, the diagnosis of PD is based on clinical symptoms and imaging studies. Although highly accurate diagnostic criteria have been published, early diagnosis is becoming increasingly important in treatment strategies for neurodegenerative diseases. Here, we also describe biomarkers that our group is working on.

自 1998 年发现家族性帕金森病 (PD) Parkin（现为PRKN ）的致病基因以来，已经过去了 25 年。PRKN是年轻发病帕金森病最常见的致病基因。Parkin 编码泛素蛋白连接酶，Parkin 参与线粒体自噬（一种巨自噬），与 PTEN 诱导的激酶 1 (PINK1) 协同作用。这两种基因产物也参与线粒体质量控制。在发现的许多导致帕金森病的遗传基因中，发现PRKN是青少年发病帕金森病的一个原因，这对其他神经退行性疾病产生了显着影响。这是因为蛋白水解系统的参与已被认为是观察到包涵体形成的神经退行性疾病的常见机制。PRKN参与PD的发现引起了人们对蛋白水解系统参与神经退行性疾病的关注。我们课题组成功分离鉴定了Parkin机制中参与线粒体电子传递系统的CHCHD2和参与溶酶体系统的prosaposin（PSAP）。遗传性PD无疑是孤立性PD的重要线索，迄今为止至少报道了25个左右的基因和位点。如此多的基因表明帕金森病是一组非常多样化的疾病。目前，PD的诊断基于临床症状和影像学检查。尽管高度准确的诊断标准已经发布，但早期诊断在神经退行性疾病的治疗策略中变得越来越重要。在这里，我们还描述了我们小组正在研究的生物标志物。