Mechanism of neuronal death induced by oxidative stress in Parkinson's disease

帕金森病(PD)是第二种最常见的与年龄相关的慢性神经退行性疾病。帕金森病多巴胺能神经元死亡的机制尚未完全阐明，但氧化应激增加可能是神经元损伤的最重要的起始者或介导者。在本研究中，我们研究了日本猕猴短暂性脑缺血再灌流后黑质(SN)蛋白的氧化损伤，以确定ROS氧化的靶蛋白。分子伴侣(热休克70k Da蛋白1、T-复合体蛋白1亚单位α等)、能量代谢相关酶(线粒体乌头酸酶、谷氨酸脱氢酶1等)和结构蛋白(二氢嘧啶酶相关蛋白2等)的羰基水平增加。因此，SN中这些蛋白的氧化损伤可能导致神经保护功能的丧失，从而导致神经元死亡。此外，这些蛋白的甲基化可作为评估氧化应激所致神经细胞死亡的生物标志物。

Parkinson's disease(PD) is the second most common, chronic age-related neurodegenerative disease. The mechanisms of cell death of dopaminergic neurons in PD have not yet been fully elucidated, but increased oxidative stress is perhaps the most important initiators or mediators of neuronal damage. In this study, to identify target proteins of reactive oxygen species(ROS) oxidation, we investigated oxidative damage of proteins in substantia nigra(SN) isolated from Japanese monkeys after transient cerebral ischemia-reperfusion. The carbonyl levels of molecular chaperones(heat shock 70k Da protein 1, T-complex protein 1 subunit alpha, etc), energy metabolism-related enzymes(mitochondrial aconitase, glutamate dehydrogenase 1, etc) and structural proteins(dihydropyrimidinase-related protein 2, etc) were increased. Therefore, oxidative damage to these proteins in SN may lead to loss of the neuroprotective function, which contributes to neuronal death. Furthermore, carbonylation of these proteins may be used as a biomarker for assessing the neuronal cell death induced by oxidative stress.