Glutathione Peroxidase 4 is associated with Neuromelanin in Substantia Nigra and Dystrophic Axons in Putamen of Parkinson's brain.
Glutathione Peroxidase 4 is associated with Neuromelanin in Substantia Nigra and Dystrophic Axons in Putamen of Parkinson's brain.
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DOI：
10.1186/1750-1326-6-8
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发表时间：
2011-01-21
影响因子：
15.1
通讯作者：
Ross GW
中科院分区：
文献类型：
--
作者：
Bellinger FP;Bellinger MT;Seale LA;Takemoto AS;Raman AV;Miki T;Manning-Boğ AB;Berry MJ;White LR;Ross GW
帕金森病是一种神经退行性疾病，其病理特征在于从中脑中的黑质投射到壳核和尾状核的黑质纹状体多巴胺神经元的损失，导致运动迟缓、僵硬和静止性震颤的临床特征。氧化多巴胺和相关化合物的氧化应激可能导致这种疾病的变性特征。为了研究磷脂氢过氧化物酶谷胱甘肽过氧化物酶4（GPX4）在保护氧化应激中的可能作用，我们研究了GPX4在有和没有帕金森病的人死后脑组织中的表达。在对照样本和帕金森病样本中，GPX 4都在与神经黑色素共存的多巴胺能黑质神经元中发现。与对照组相比，帕金森病患者黑质中的GPX 4总体显著降低，但相对于存活黑质细胞的细胞密度增加。在壳核中，GPX4集中在帕金森病受试者的营养不良的多巴胺能轴突中，尽管GPX4的总体水平与对照壳核相比没有显著差异。这项研究表明，在黑质的神经元GPX4的上调和这种蛋白质与帕金森氏症的大脑纹状体中的营养不良轴突的关联，表明可能的神经保护作用。此外，我们的研究结果表明这种酶可能有助于神经黑色素的产生。
Parkinson's disease is a neurodegenerative disorder characterized pathologically by the loss of nigrostriatal dopamine neurons that project from the substantia nigra in the midbrain to the putamen and caudate nuclei, leading to the clinical features of bradykinesia, rigidity, and rest tremor. Oxidative stress from oxidized dopamine and related compounds may contribute to the degeneration characteristic of this disease. To investigate a possible role of the phospholipid hydroperoxidase glutathione peroxidase 4 (GPX4) in protection from oxidative stress, we investigated GPX4 expression in postmortem human brain tissue from individuals with and without Parkinson's disease. In both control and Parkinson's samples, GPX4 was found in dopaminergic nigral neurons colocalized with neuromelanin. Overall GPX4 was significantly reduced in substantia nigra in Parkinson's vs. control subjects, but was increased relative to the cell density of surviving nigral cells. In putamen, GPX4 was concentrated within dystrophic dopaminergic axons in Parkinson's subjects, although overall levels of GPX4 were not significantly different compared to control putamen. This study demonstrates an up-regulation of GPX4 in neurons of substantia nigra and association of this protein with dystrophic axons in striatum of Parkinson's brain, indicating a possible neuroprotective role. Additionally, our findings suggest this enzyme may contribute to the production of neuromelanin.
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DOI：
10.1073/pnas.97.22.11869
发表时间：
2000-10-24
影响因子：
11.1
作者：
Sulzer, D;Bogulavsky, J;Zecca, L
通讯作者：
Zecca, L
影响因子：
2.9
作者：
Mouton, PR;Long, JM;Ingram, DK
通讯作者：
Ingram, DK
DOI：
10.1016/j.biocel.2004.09.009
发表时间：
2005-05-01
影响因子：
4
作者：
Chinta, SJ;Andersen, JK
通讯作者：
Andersen, JK
影响因子：
--
作者：
AMBANI, LM;VANWOERT, MH;MURPHY, S
通讯作者：
MURPHY, S
影响因子：
11.2
作者：
Ross, GW;Petrovitch, H;White, LR
通讯作者：
White, LR