Mitochondrial dysfunction in movement disorders.
Mitochondrial dysfunction in movement disorders.
复制标题
运动障碍中的线粒体功能障碍。
DOI：
10.1097/00019052-199408000-00010
复制
发表时间：
1994
影响因子：
4.8
通讯作者：
Beal,MF
中科院分区：
文献类型：
--
作者：
Schulz,JB;Beal,MF
关于几种运动障碍中神经元变性机制的主要理论是线粒体缺陷可能起作用。帕金森氏病、亨廷顿氏病、多系统萎缩和特发性肌张力障碍的生化研究表明，死后脑组织、血小板、肌肉或淋巴细胞中氧化磷酸化酶存在缺陷。基底神经节和黑质也特别容易受到年龄依赖性线粒体DNA缺失的累积的影响，这可能导致运动障碍的延迟发作。帕金森病的1-甲基-4-苯基-1，2，3，6-四氢-吡啶模型涉及转化为1-甲基-4-苯基-吡啶鎓，其然后抑制电子传递链的复合物I。我们的研究表明，复合物II抑制剂3-硝基丙酸可以密切复制亨廷顿病的神经化学，组织学和临床特征。在这两种模型中神经元死亡的机制可能是缓慢的兴奋毒性。因此，直接的生化研究和运动障碍的动物模型都表明，线粒体功能障碍可能在其发病机制中发挥直接作用。
A major theory regarding the mechanism of neuronal degeneration in several movement disorders is that mitochondrial defects may play a role. Biochemical studies in Parkinson's disease, Huntington's disease, multiple system atrophy, and idiopathic dystonia have shown defects in enzymes of oxidative phosphorylation in postmortem brain tissue, platelets, muscle, or lymphocytes. The basal ganglia and substantia nigra are also particularly susceptible to the accumulation of age-dependent mitochondrial DNA deletions, which may contribute to the delayed onset of movement disorders. The 1-methyl-4-phenyl 1, 2, 3, 6-tetrahydro-pyridine model of Parkinson's disease involves conversion to 1-methyl-4-pheny-Ipyridinium, which then inhibits complex I of the electron transport chain. Our studies show that the complex II inhibitor 3-nitropropionic acid can closely replicate the neurochemical, histologic, and clinical features of Huntington's disease. The mechanism of neuronal death in both these models may be slow excitotoxicity. Both direct biochemical studies and animal models of movement disorders therefore suggest that mitochondrial dysfunction may play a direct role in their pathogenesis.