Cell and Molecular Biology Department, John A, Burns School of Medicine, University of Hawaii, Honolulu, HI 96813 USA.
Mol Neurodegener. 2011 Jan 21;6(1):8. doi: 10.1186/1750-1326-6-8.
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.
帕金森病是一种神经退行性疾病，其病理特征是从中脑黑质投射到纹状体和尾状核的黑质多巴胺能神经元丧失，导致运动迟缓、僵硬和静止性震颤等临床特征。氧化应激可能导致这种疾病的特征性退化。
为了研究磷脂氢过氧化物谷胱甘肽过氧化物酶 4（GPX4）在抗氧化应激中的可能作用，我们研究了帕金森病患者和非帕金森病患者死后人脑组织中的 GPX4 表达。在对照组和帕金森病组中，GPX4 均存在于多巴胺能黑质神经元中，与神经黑色素共定位。与对照组相比，帕金森病患者的黑质中总 GPX4 明显减少，但与存活的黑质细胞密度相比相对增加。在纹状体中，GPX4 集中在帕金森病患者的变性多巴胺能轴突内，尽管与对照组纹状体相比，总 GPX4 水平没有显著差异。
本研究表明，GPX4 在黑质神经元中上调，并与帕金森病大脑纹状体中的变性轴突相关，表明其可能具有神经保护作用。此外，我们的发现表明，该酶可能有助于神经黑色素的产生。
