Glutathione, iron and Parkinson's disease
Glutathione, iron and Parkinson's disease
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DOI：
10.1016/s0006-2952(02)01174-7
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发表时间：
2002-09-01
影响因子：
5.8
通讯作者：
Andersen, JK
中科院分区：
文献类型：
--
作者：
Bharath, S;Hsu, M;Andersen, JK
帕金森病(PD)是一种进行性神经衰退性疾病，涉及中脑黑质(SN)多巴胺能神经元的神经变性。氧化应激被认为在帕金森病相关的神经细胞死亡中起主要作用。重要的是，PD患者SN中的硫醇三肽谷胱甘肽的胞浆水平急剧下降。谷胱甘肽(GSH)在大脑中具有多种功能，主要是作为抗氧化剂和氧化还原调节剂。谷胱甘肽耗竭可能通过选择性抑制线粒体复合体I活性而影响线粒体功能。帕金森病期间神经退行性变的一个重要生化特征是存在异常的蛋白质聚集物，即胞浆内的路易小体。GSH耗竭引起的氧化损伤也可能通过损害泛素-蛋白酶体蛋白降解途径，加速缺陷蛋白的积聚，导致黑质多巴胺能神经元的细胞死亡。补充大脑内正常的谷胱甘肽水平可能是治疗帕金森病的重要关键。一些报告表明，SN患者体内的铁积累也可能导致PD期间的氧化应激。(C)2002 Elsevier Science Inc.保留所有权利。
Parkinson's disease (PD) is a progressive neurodegencrative disease involving neurodegeneration of dopaminergic neurons of the substantia nigra (SN), a part of the midbrain. Oxidative stress has been implicated to play a major role in the neuronal cell death associated with PD. Importantly, there is a drastic depletion in cytoplasmic levels of the thiol tripeptide glutathione within the SN of PD patients. Glutathione (GSH) exhibits several functions in the brain chiefly acting as an antioxidant and a redox regulator. GSH depletion has been shown to affect mitochondrial function probably via selective inhibition of mitochondrial complex I activity. An important biochemical feature of neurodegeneration during PD is the presence of abnormal protein aggregates present as intracytoplasmic inclusions called Lewy bodies. Oxidative damage via GSH depletion might also accelerate the build-up of defective proteins leading to cell death of SN dopaminergic neurons by impairing the ubiquitin-proteasome pathway of protein degradation. Replenishment of normal glutathione levels within the brain may hold an important key to therapeutics for PD. Several reports have suggested that iron accumulation in the SN patients might also contribute to oxidative stress during PD. (C) 2002 Elsevier Science Inc. All rights reserved.