Protein aggregation in the pathogenesis of familial and sporadic Parkinson's disease
Protein aggregation in the pathogenesis of familial and sporadic Parkinson's disease
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DOI：
10.1016/j.neurobiolaging.2005.08.012
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发表时间：
2006-04-01
影响因子：
4.2
通讯作者：
Olanow, CW
中科院分区：
文献类型：
--
作者：
McNaught, KSP;Olanow, CW
帕金森病（Parkinson's disease，PD）是一种缓慢进展的、与年龄相关的神经退行性疾病。神经元死亡的原因和机制一直难以捉摸。然而，最近的遗传，尸检和实验证据表明，蛋白质的积累和聚集是突出发生在散发性和家族性PD。这些事件与其他细胞和生物化学变化以及神经退行性过程的相关性正在解开。越来越明显的是，一种或多种缺陷，包括突变、氧化应激、线粒体损伤和泛素-蛋白酶体系统功能障碍，导致PD中异常蛋白的过量产生和聚集。在这方面，改变蛋白质处理似乎是一个中心因素的致病过程中发生的各种遗传性和散发性形式的PD。这表明，操纵蛋白水解系统是一个合理的方法，在发展的神经保护疗法，可以修改病理过程中的PD。(C)2005年爱思唯尔公司All rights reserved.
Parkinson's disease (PD) is a slowly progressive, age-related, neurodegenerative disorder. The cause and mechanism of neuronal death have been elusive. However, recent genetic, postmortem and experimental evidence show that protein accumulation and aggregation are prominent occurrences in both sporadic and familial PD. The relevance of these events to other cellular and biochemical changes, and to the neurodegenerative process, is being unraveled. It is increasingly evident that one or a combination of defects, including mutations, oxidative stress, mitochondrial impairment and dysfunction of the ubiquitin-proteasome system, lead to an excess production and aggregation of abnormal proteins in PD. In this respect, altered protein handling appears to be a central factor in the pathogenic process occurring in the various hereditary and sporadic forms of PD. This suggests that manipulation of proteolytic systems is a rational approach in the development of neuroprotective therapies that could modify the pathological course of PD. (C) 2005 Elsevier Inc. All rights reserved.