Insights in pathogenesis of multiple sclerosis: nitric oxide may induce mitochondrial dysfunction of oligodendrocytes
Insights in pathogenesis of multiple sclerosis: nitric oxide may induce mitochondrial dysfunction of oligodendrocytes
复制标题
多发性硬化症发病机制的见解：一氧化氮可能诱导少突胶质细胞线粒体功能障碍。
DOI：
10.1515/revneuro-2017-0033
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发表时间：
2018-01-01
影响因子：
4.1
通讯作者：
Yao, Zhongxiang
中科院分区：
文献类型：
--
作者：
Lan, Minghong;Tang, Xiaoyi;Yao, Zhongxiang
脱髓鞘疾病，如多发性硬化症(MS)，是中枢神经系统(CNS)的常见病，起源于髓鞘丢失和轴突损伤。少突胶质细胞功能障碍是中枢神经系统脱髓鞘病变的直接原因。一氧化氮(NO)在脱髓鞘疾病的病理过程中起重要作用。尽管NO的神经毒性更可能是由过氧亚硝酸盐而不是NO本身介导的，但NO可以通过介导线粒体DNA、线粒体膜和线粒体呼吸链复合体的损伤来损害少突胶质细胞的能量代谢。在MS的发展过程中，NO主要介导脱髓鞘、轴突变性和细胞死亡。因此，在本综述中，我们广泛讨论了NO在少突胶质细胞中的危害，它被认为是脱髓鞘疾病的主要介质，例如MS。我们假设NO通过损害单羧酸转运体1的功能，特别是引起轴突变性来参与MS的发生。因此，它进一步提供了一个新的见解，即对于OL，NO可能是改善脱髓鞘疾病病程的可靠治疗靶点。
Demyelinating diseases, such as multiple sclerosis (MS), are kinds of common diseases in the central nervous system (CNS), and originated from myelin loss and axonal damage. Oligodendrocyte dysfunction is the direct reason of demyelinating lesions in the CNS. Nitric oxide (NO) plays an important role in the pathological process of demyelinating diseases. Although the neurotoxicity of NO is more likely mediated by peroxynitrite rather than NO itself, NO can impair oligodendrocyte energy metabolism through mediating the damaging of mitochondrial DNA, mitochondrial membrane and mitochondrial respiratory chain complexes. In the progression of MS, NO can mainly mediate demyelination, axonal degeneration and cell death. Hence, in this review, we extensively discuss endangerments of NO in oligodendrocytes (OLs), which is suggested to be the main mediator in demyelinating diseases, e.g. MS. We hypothesize that NO takes part in MS through impairing the function of monocarboxylate transporter 1, especially causing axonal degeneration. Then, it further provides a new insight that NO for OLs may be a reliable therapeutic target to ameliorate the course of demyelinating diseases.