Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York, New York 10065, USA.
Mov Disord. 2010;25 Suppl 1(Suppl 1):S155-60. doi: 10.1002/mds.22781.
Parkinson's disease (PD) is marked by widespread neurodegeneration in the brain in addition to a selective yet prominent and progressive loss of nigrostriatal dopaminergic neurons. Of the multiple theories suggested in the pathogenesis of PD, mitochondrial dysfunction takes a center stage in both sporadic and familial forms of illness. Deficits in mitochondrial functions due to impaired bioenergetics, aging associated increased generation of reactive oxygen species, damage to mitochondrial DNA, impaired calcium buffering, and alterations in mitochondrial morphology may contribute to improper functioning of the CNS leading to neurodegeneration. These mitochondrial alterations suggest that a potential target worth exploring for neuroprotective therapies are the ones that can preserve mitochondrial functions in PD. Here, we provide a recent update on potential drugs that are known to block mitochondrial dysfunctions in various experimental models and those that are currently under clinical trials for PD. We also review novel mitochondrial survival pathways that provide hope and promise for innovative neuroprotective therapies in the future that can be explored as possible therapeutic intervention for PD pathogenesis.
帕金森病（PD）除了黑质纹状体多巴胺能神经元选择性且显著进行性丧失外，还以大脑广泛的神经退行性变为特征。在 PD 的发病机制中提出的多种理论中，线粒体功能障碍在散发性和家族性疾病中都占据中心地位。由于生物能受损、与衰老相关的活性氧生成增加、线粒体 DNA 损伤、钙缓冲受损以及线粒体形态改变导致的线粒体功能缺陷，可能导致中枢神经系统功能异常，从而导致神经退行性变。这些线粒体改变表明，对于神经保护治疗，有一个值得探索的潜在靶点，即能够维持 PD 中线粒体功能的药物。在这里，我们提供了最新的关于已知能够阻断各种实验模型中线粒体功能障碍的潜在药物的信息，以及目前正在进行的针对 PD 的临床试验的信息。我们还回顾了新的线粒体存活途径，为未来创新的神经保护治疗提供了希望和承诺，这些治疗方法可能作为 PD 发病机制的潜在治疗干预措施进行探索。
