Department of Neurology, Anhui Provincial Hospital, Anhui Medical University, Hefei, Anhui Province 230001, PR China; Department of Neurology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230001, PR China.
Department of Neurology, Anhui Provincial Hospital, Anhui Medical University, Hefei, Anhui Province 230001, PR China.
Mitochondrion. 2019 Nov;49:35-45. doi: 10.1016/j.mito.2019.07.003. Epub 2019 Jul 6.
Mitochondrial dysfunction is becoming one of the most emerging pathological process in the etiology of neurological disorders. Other common etiologies of the neurological disorders are aging and oxidative stress. Neurodegenerative disorders for instance Huntington's disease, Parkinson's disease, Amyotrophic lateral sclerosis, Epilepsy, Schizophrenia, Multiple sclerosis, Neuropathic pain and Alzheimer's disease involves mitochondrial dysfunction and is regarded as the core of their pathological processes. Most central pathological feature of the neurodegenerative diseases is apoptosis which is regulated by mitochondria. Altered signaling of the apoptotic mechanisms are involved in neurodegeneration. Abnormal levels of these molecular apoptotic proteins promotes the pathogenesis of neurological disorders. Mitochondria are also implicated in the production of reactive oxygen species (ROS). Raised ROS levels initiates the cascade leading to the non-apoptotic death of cells. ROS produced in cells acts as signaling molecules, but when produced in abundance will result in cellular consequences to deoxyribonucleic acid, proteins and lipids, decreased effectiveness of cellular mechanisms, initiation of inflammatory pathways, excitotoxicity, protein agglomeration and apoptosis. Protecting mitochondrial function has been identified as the most effective therapeutic approach to attenuate the pathogenesis of neurodegenerative diseases. This review aims to provide an insight into the mitochondrial dysfunction in the pathogenesis of neurological disorders, alteration in signaling cascades of apoptosis in mitochondrial dysfunction and the therapeutic strategies (both natural and synthetic drugs) targeting these mitochondrial apoptotic pathways and oxidative stress that holds great promise.
线粒体功能障碍正在成为神经紊乱病因学中最新兴的病理过程之一。神经紊乱的其他常见病因是衰老和氧化应激。神经退行性疾病，如亨廷顿病、帕金森病、肌萎缩侧索硬化症、癫痫、精神分裂症、多发性硬化症、神经病理性疼痛和阿尔茨海默病，都涉及线粒体功能障碍，并被视为其病理过程的核心。大多数神经退行性疾病的中心病理特征是由线粒体调节的细胞凋亡。凋亡机制的信号改变参与了神经退行性变。这些分子凋亡蛋白水平的异常促进了神经紊乱的发病机制。线粒体也参与了活性氧物质（ROS）的产生。ROS 水平的升高引发了导致细胞非凋亡性死亡的级联反应。细胞中产生的 ROS 作为信号分子发挥作用，但当过量产生时，会导致脱氧核糖核酸、蛋白质和脂质的细胞后果减少，细胞机制的有效性降低，炎症途径的启动，兴奋毒性，蛋白质聚集和细胞凋亡。保护线粒体功能已被确定为减轻神经退行性疾病发病机制的最有效治疗方法。这篇综述旨在深入了解线粒体功能障碍在神经紊乱发病机制中的作用、线粒体功能障碍中凋亡信号级联的改变，以及针对这些线粒体凋亡途径和氧化应激的治疗策略（天然和合成药物），这些策略具有很大的潜力。
