Rajda Cecilia, Pukoli Dániel, Bende Zsuzsanna, Majláth Zsófia, Vécsei László
Department of Neurology, University of Szeged, 6725 Szeged, Hungary.
Department of Neurology, Vaszary Kolos Hospital, 2500 Esztergom, Hungary.
Int J Mol Sci. 2017 Feb 8;18(2):353. doi: 10.3390/ijms18020353.
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS). There is increasing evidence that MS is not only characterized by immune mediated inflammatory reactions, but also by neurodegenerative processes. There is cumulating evidence that neurodegenerative processes, for example mitochondrial dysfunction, oxidative stress, and glutamate (Glu) excitotoxicity, seem to play an important role in the pathogenesis of MS. The alteration of mitochondrial homeostasis leads to the formation of excitotoxins and redox disturbances. Mitochondrial dysfunction (energy disposal failure, apoptosis, etc.), redox disturbances (oxidative stress and enhanced reactive oxygen and nitrogen species production), and excitotoxicity (Glu mediated toxicity) may play an important role in the progression of the disease, causing axonal and neuronal damage. This review focuses on the mechanisms of mitochondrial dysfunction (including mitochondrial DNA (mtDNA) defects and mitochondrial structural/functional changes), oxidative stress (including reactive oxygen and nitric species), and excitotoxicity that are involved in MS and also discusses the potential targets and tools for therapeutic approaches in the future.
多发性硬化症（MS）是一种中枢神经系统（CNS）的慢性炎症性疾病。越来越多的证据表明，MS不仅以免疫介导的炎症反应为特征，还以神经退行性过程为特征。有越来越多的证据表明，神经退行性过程，例如线粒体功能障碍、氧化应激和谷氨酸（Glu）兴奋性毒性，似乎在MS的发病机制中起重要作用。线粒体稳态的改变导致兴奋性毒素的形成和氧化还原紊乱。线粒体功能障碍（能量处理失败、细胞凋亡等）、氧化还原紊乱（氧化应激以及活性氧和氮物种产生增加）和兴奋性毒性（Glu介导的毒性）可能在疾病进展中起重要作用，导致轴突和神经元损伤。本综述重点关注与MS相关的线粒体功能障碍机制（包括线粒体DNA（mtDNA）缺陷和线粒体结构/功能变化）、氧化应激（包括活性氧和氮物种）以及兴奋性毒性，并讨论未来治疗方法的潜在靶点和工具。
