Jagatha Balusamy, Mythri Rajeswara Babu, Vali Shireen, Bharath M M Srinivas
Department of Neurochemistry, National Institute of Mental Health and Neurosciences, 2900 Hosur Road, Bangalore, Karnataka, India.
Free Radic Biol Med. 2008 Mar 1;44(5):907-17. doi: 10.1016/j.freeradbiomed.2007.11.011. Epub 2007 Dec 4.
Oxidative stress has been implicated in the degeneration of dopaminergic neurons in the substantia nigra (SN) of Parkinson's disease (PD) patients. An important biochemical feature of presymptomatic PD is a significant depletion of the thiol antioxidant glutathione (GSH) in these neurons resulting in oxidative stress, mitochondrial dysfunction, and ultimately cell death. We have earlier demonstrated that curcumin, a natural polyphenol obtained from turmeric, protects against peroxynitrite-mediated mitochondrial dysfunction both in vitro and in vivo. Here we report that treatment of dopaminergic neuronal cells and mice with curcumin restores depletion of GSH levels, protects against protein oxidation, and preserves mitochondrial complex I activity which normally is impaired due to GSH loss. Using systems biology and dynamic modeling we have explained the mechanism of curcumin action in a model of mitochondrial dysfunction linked to GSH metabolism that corroborates the major findings of our experimental work. These data suggest that curcumin has potential therapeutic value for neurodegenerative diseases involving GSH depletion-mediated oxidative stress.
氧化应激与帕金森病（PD）患者黑质（SN）中多巴胺能神经元的变性有关。症状前PD的一个重要生化特征是这些神经元中的硫醇抗氧化剂谷胱甘肽（GSH）显著耗竭，导致氧化应激、线粒体功能障碍，并最终导致细胞死亡。我们之前已经证明，姜黄素是一种从姜黄中提取的天然多酚，在体外和体内都能防止过氧亚硝酸盐介导的线粒体功能障碍。在此我们报告，用姜黄素处理多巴胺能神经元细胞和小鼠可恢复GSH水平的耗竭，防止蛋白质氧化，并保留线粒体复合物I的活性，该活性通常因GSH丧失而受损。使用系统生物学和动态建模，我们在与GSH代谢相关的线粒体功能障碍模型中解释了姜黄素的作用机制，这证实了我们实验工作的主要发现。这些数据表明，姜黄素对涉及GSH耗竭介导的氧化应激的神经退行性疾病具有潜在的治疗价值。
