Zeevalk G D, Bernard L P, Song C, Gluck M, Ehrhart J
Department of Neurology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA.
Antioxid Redox Signal. 2005 Sep-Oct;7(9-10):1117-39. doi: 10.1089/ars.2005.7.1117.
Although the etiology for many neurodegenerative diseases is unknown, the common findings of mitochondrial defects and oxidative damage posit these events as contributing factors. The temporal conundrum of whether mitochondrial defects lead to enhanced reactive oxygen species generation, or conversely, if oxidative stress is the underlying cause of the mitochondrial defects remains enigmatic. This review focuses on evidence to show that either event can lead to the evolution of the other with subsequent neuronal cell loss. Glutathione is a major antioxidant system used by cells and mitochondria for protection and is altered in a number of neurodegenerative and neuropathological conditions. This review also addresses the multiple roles for glutathione during mitochondrial inhibition or oxidative stress. Protein aggregation and inclusions are hallmarks of a number of neurodegenerative diseases. Recent evidence that links protein aggregation to oxidative stress and mitochondrial dysfunction will also be examined. Lastly, current therapies that target mitochondrial dysfunction or oxidative stress are discussed.
尽管许多神经退行性疾病的病因尚不清楚，但线粒体缺陷和氧化损伤的常见发现表明这些事件是促成因素。线粒体缺陷是否会导致活性氧生成增加，或者相反，氧化应激是否是线粒体缺陷的根本原因，这个时间难题仍然是个谜。本综述着重于证据表明，这两种情况中的任何一种都可能导致另一种情况的演变，随后导致神经元细胞丢失。谷胱甘肽是细胞和线粒体用于保护的主要抗氧化系统，并且在许多神经退行性和神经病理学病症中会发生改变。本综述还探讨了谷胱甘肽在线粒体抑制或氧化应激期间的多种作用。蛋白质聚集和包涵体是许多神经退行性疾病的标志。最近将蛋白质聚集与氧化应激和线粒体功能障碍联系起来的证据也将进行研究。最后，讨论了针对线粒体功能障碍或氧化应激的当前疗法。
