Department of Neurology Kyoto University Graduate School of Medicine, Kyoto, Japan.
Department of Neurology Kyoto University Graduate School of Medicine, Kyoto, Japan.
Neurosci Lett. 2021 Nov 20;765:136267. doi: 10.1016/j.neulet.2021.136267. Epub 2021 Sep 24.
For the development of disease-modifying therapies for Parkinson's disease (PD) the identification of biomarkers in the prodromal stage is urgently required. Because PD is considered a systemic disease even in the early stage, we performed a metabolomic analysis of the plasma from a mouse model of prodromal PD (p-PD). Increased levels of isobutyrylcarnitine in p-PD mice imply an abnormality in β-oxidation in mitochondria, and increased levels of pyrimidine nucleoside can be associated with mitochondrial dysfunction. Consistent with these results, the immunoblot analysis showed a defect in mitochondrial complex I assembly in p-PD mice. These results suggest that systemic mitochondrial dysfunction may exist in p-PD mice and contribute to the pathogenesis of PD, potentially being useful as early biomarkers for PD.
为了开发治疗帕金森病（PD）的疾病修饰疗法，迫切需要在前驱期识别生物标志物。由于 PD 甚至在早期阶段就被认为是一种系统性疾病，因此我们对前驱期 PD （p-PD）小鼠模型的血浆进行了代谢组学分析。p-PD 小鼠中异丁酰肉碱水平升高表明线粒体中的β-氧化异常，嘧啶核苷水平升高可能与线粒体功能障碍有关。与这些结果一致，免疫印迹分析显示 p-PD 小鼠中线粒体复合物 I 组装存在缺陷。这些结果表明，系统性线粒体功能障碍可能存在于 p-PD 小鼠中，并有助于 PD 的发病机制，可能作为 PD 的早期生物标志物。
