Mitochondrial dysfunction in a mouse model of prodromal Parkinson’s disease: A metabolomic analysis
Mitochondrial dysfunction in a mouse model of prodromal Parkinson’s disease: A metabolomic analysis
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前驱帕金森病小鼠模型的线粒体功能障碍：代谢组学分析
DOI：
10.1016/j.neulet.2021.136267
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发表时间：
2021
影响因子：
2.5
通讯作者：
Takahashi Ryosuke
中科院分区：
文献类型：
--
作者：
Ikuno Masashi;Yamakado Hodaka;Amano Ikuko;Hatanaka Yusuke;Uemura Norihito;Matsuzawa Shu-ichi;Takahashi Ryosuke
为了开发帕金森病（PD）的疾病修饰疗法，迫切需要识别前驱期的生物标志物。由于PD被认为是一种全身性疾病，即使在早期阶段，我们进行了代谢组学分析的血浆从前驱PD（p-PD）的小鼠模型。p-PD小鼠中异丁酰肉碱水平的增加暗示线粒体中β-氧化的异常，并且嘧啶核苷水平的增加可能与线粒体功能障碍相关。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，并有助于PD的发病机制，可能是有用的早期生物标志物PD。
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.