Patel Jaimin, 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, USA.
Department of Neurosurgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
CNS Drugs. 2022 Dec;36(12):1249-1267. doi: 10.1007/s40263-022-00973-7. Epub 2022 Nov 15.
Parkinson's disease is the second most prevalent neurodegenerative disease and contributes significantly to morbidity globally. Currently, no disease-modifying therapies exist to combat this disorder. Insights from the molecular and cellular pathobiology of the disease seems to indicate promising therapeutic targets. The parkin protein has been extensively studied for its role in autosomal recessive Parkinson's disease and, more recently, its role in sporadic Parkinson's disease. Parkin is an E3 ubiquitin ligase that plays a prominent role in mitochondrial quality control, mitochondrial-dependent cell death pathways, and other diverse functions. Understanding the numerous roles of parkin has introduced many new possibilities for therapeutic modalities in treating both autosomal recessive Parkinson's disease and sporadic Parkinson's disease. In this article, we review parkin biology with an emphasis on mitochondrial-related functions and propose novel, potentially disease-modifying therapeutic approaches for treating this debilitating condition.
帕金森病是全球第二常见的神经退行性疾病，对全球发病率有重大影响。目前，尚无改变疾病进程的疗法来对抗这种疾病。该疾病分子和细胞病理生物学的见解似乎表明了有前景的治疗靶点。帕金蛋白因其在常染色体隐性帕金森病中的作用，以及最近在散发性帕金森病中的作用而受到广泛研究。帕金是一种E3泛素连接酶，在线粒体质量控制、线粒体依赖性细胞死亡途径及其他多种功能中发挥重要作用。了解帕金的众多作用为治疗常染色体隐性帕金森病和散发性帕金森病的治疗方式带来了许多新的可能性。在本文中，我们回顾帕金生物学，重点关注与线粒体相关的功能，并提出治疗这种使人衰弱疾病的新型、可能改变疾病进程的治疗方法。
