Somatic mtDNA variation is an important component of Parkinson's disease
Somatic mtDNA variation is an important component of Parkinson's disease
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DOI：
10.1016/j.neurobiolaging.2015.10.036
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发表时间：
2016-02-01
影响因子：
4.2
通讯作者：
Hudson, Gavin
中科院分区：
文献类型：
--
作者：
Coxhead, Jonathan;Kurzawa-Akanbi, Marzena;Hudson, Gavin
越来越多的证据表明，通过遗传性线粒体DNA （mtDNA）变异或线粒体蛋白质组学缺陷介导的线粒体功能障碍与帕金森病（PD）有关。然而，尽管如此，体细胞mtDNA点突变，特别是点突变负担在PD中的作用尚不清楚。在这里，我们利用最新的技术和方法进步，在迄今为止最大规模的死后PD组织mtDNA研究中，研究年龄相关和获得性mtDNA突变的作用。我们的数据显示，与匹配的对照组相比，PD患者的mtDNA突变负担增加，但不限于黑质致密部。这种突变负担在编码细胞色素c氧化酶的基因中似乎有所增加，这支持了先前PD中线粒体功能障碍的蛋白质研究。接受实验的局限性，我们的研究证实了年龄相关mtDNA点突变在PD病因学中的重要作用，并且通过分析2个不同的大脑区域，我们能够表明PD患者的大脑总体上更容易受到mtDNA突变的影响。(C) 2016年作者。Elsevier Inc.出版。这是一篇基于CC BY许可的开放获取文章。
There is a growing body of evidence linking mitochondrial dysfunction, mediated either through inherited mitochondrial DNA (mtDNA) variation or mitochondrial proteomic deficit, to Parkinson's disease (PD). Yet, despite this, the role of somatic mtDNA point mutations and specifically point-mutational burden in PD is poorly understood. Here, we take advantage of recent technical and methodological advances to examine the role of age-related and acquired mtDNA mutation in the largest study of mtDNA in postmortem PD tissue to date. Our data show that PD patients suffer an increase in mtDNA mutational burden in, but no limited to, the substantia nigra pars compacta when compared to matched controls. This mutational burden appears increased in genes encoding cytochrome c oxidase, supportive of previous protein studies of mitochondrial dysfunction in PD. Accepting experimental limitations, our study confirms the important role of age-related mtDNA point mutation in the etiology of PD, moreover, by analyzing 2 distinct brain regions, we are able to show that PD patient brains are more vulnerable to mtDNA mutation overall. (C) 2016 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license.