Di Monte D A
California Institute for Medical Research, San Jose 95128.
Neurology. 1991 May;41(5 Suppl 2):38-42; discussion 42-3. doi: 10.1212/wnl.41.5_suppl_2.38.
Two major lines of evidence support the hypothesis that an impairment of mitochondrial function may underlie neuronal death in Parkinson's disease. First, the neurotoxicity of the parkinsonism-inducing compound 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is due to the generation of its 1-methyl-4-phenylpyridinium (MPP+) metabolite in the central nervous system; the toxicity of MPP+ is likely to result from its ability to block mitochondrial electron flow at the level of complex I. Second, recent studies have revealed a deficiency of mitochondrial complex I activity in the brain as well as other tissues of parkinsonian patients. This enzyme activity reduction might be explained by a defect in one or more of the genes coding for the subunits of complex I. Since seven of these genes are localized in the mitochondrial genome, it is conceivable that abnormal mitochondrial DNA (mtDNA) might play a role in the pathogenesis of Parkinson's disease. The entire sequence of the human mitochondrial genome is known, and human mtDNA can be isolated and rapidly analyzed using techniques such as the polymerase chain reaction. Therefore, identification of an easily detectable mtDNA alteration might ultimately be used as a marker for the diagnosis and screening of Parkinson's disease.
有两大证据支持线粒体功能受损可能是帕金森病神经元死亡基础的假说。首先，诱发帕金森症的化合物1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）的神经毒性是由于其在中枢神经系统中生成了1-甲基-4-苯基吡啶离子（MPP+）代谢产物；MPP+的毒性可能源于其在复合体I水平阻断线粒体电子传递的能力。其次，最近的研究表明帕金森病患者大脑及其他组织中线粒体复合体I活性存在缺陷。这种酶活性降低可能是由于编码复合体I亚基的一个或多个基因存在缺陷。由于其中七个基因定位于线粒体基因组，因此可以推测异常线粒体DNA（mtDNA）可能在帕金森病的发病机制中起作用。人类线粒体基因组的完整序列是已知的，并且可以使用聚合酶链反应等技术分离和快速分析人类mtDNA。因此，识别一种易于检测的mtDNA改变最终可能用作帕金森病诊断和筛查的标志物。
