Dawson Ted M, Dawson Valina L
Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Science. 2003 Oct 31;302(5646):819-22. doi: 10.1126/science.1087753.
Parkinson's disease (PD) is a complex disorder with many different causes, yet they may intersect in common pathways, raising the possibility that neuroprotective agents may have broad applicability in the treatment of PD. Current evidence suggests that mitochondrial complex I inhibition may be the central cause of sporadic PD and that derangements in complex I cause alpha-synuclein aggregation, which contributes to the demise of dopamine neurons. Accumulation and aggregation of alpha-synuclein may further contribute to the death of dopamine neurons through impairments in protein handling and detoxification. Dysfunction of parkin (a ubiquitin E3 ligase) and DJ-1 could contribute to these deficits. Strategies aimed at restoring complex I activity, reducing oxidative stress and alpha-synuclein aggregation, and enhancing protein degradation may hold particular promise as powerful neuroprotective agents in the treatment of PD.
帕金森病（PD）是一种病因多样的复杂疾病，但其病因可能在共同途径中相互交叉，这增加了神经保护剂在PD治疗中具有广泛适用性的可能性。目前的证据表明，线粒体复合体I抑制可能是散发性PD的主要病因，复合体I紊乱导致α-突触核蛋白聚集，这促使多巴胺能神经元死亡。α-突触核蛋白的积累和聚集可能通过蛋白质处理和解毒功能受损进一步导致多巴胺能神经元死亡。帕金森蛋白（一种泛素E3连接酶）和DJ-1功能障碍可能导致这些缺陷。旨在恢复复合体I活性、减少氧化应激和α-突触核蛋白聚集以及增强蛋白质降解的策略，作为治疗PD的强大神经保护剂可能特别有前景。
