Olanow C Warren, McNaught Kevin St P
Department of Neurology, Mount Sinai School of Medicine, New York, New York10029, USA.
Mov Disord. 2006 Nov;21(11):1806-23. doi: 10.1002/mds.21013.
Increasing genetic, pathological, and experimental evidence suggest that neurodegeneration in both familial and sporadic forms of Parkinson's disease (PD) may be related to a defect in the capacity of the ubiquitin-proteasome system (UPS) to clear unwanted proteins, resulting in protein accumulation, aggregation, and cytotoxicity. This concept is supported by in vitro and in vivo laboratory experiments which show that inhibition of UPS function can cause neurodegeneration coupled with the formation of Lewy body-like inclusions. This hypothesis could account for the presence of protein aggregates and Lewy bodies in PD, the other biochemical features seen in the disorder, and the age-related vulnerability of the substantia nigra pars compacta. It also suggests novel targets for putative neuroprotective therapies for PD.
越来越多的遗传学、病理学及实验证据表明，帕金森病（PD）的家族性和散发性形式中的神经退行性变可能与泛素-蛋白酶体系统（UPS）清除不需要的蛋白质的能力缺陷有关，从而导致蛋白质积累、聚集和细胞毒性。体外和体内实验室实验支持了这一概念，这些实验表明抑制UPS功能可导致神经退行性变并伴有路易小体样包涵体的形成。这一假说可以解释PD中蛋白质聚集体和路易小体的存在、该疾病中出现的其他生化特征以及黑质致密部与年龄相关的易损性。它还为PD的潜在神经保护疗法提出了新的靶点。
