人类神经退行性疾病中线粒体DNA缺失的区域特异性分析。

Region-specific analysis of mitochondrial DNA deletions in neurodegenerative disorders in humans.

作者信息

Mawrin Christian, Kirches Elmar, Krause Guido, Schneider-Stock Regine, Bogerts Bernhard, Vorwerk Christian K, Dietzmann Knut

机构信息

Department of Neuropathology, Otto-von-Guericke-University, Leipziger Strasse 44, D-39120 Magdeburg, Germany.

出版信息

Neurosci Lett. 2004 Mar 4;357(2):111-4. doi: 10.1016/j.neulet.2003.11.073.

DOI:10.1016/j.neulet.2003.11.073

PMID:15036587

Abstract

Mitochondrial dysfunction caused by mitochondrial DNA (mtDNA) aberrations has been implicated in the neuronal death in neurodegenerative disorders. Significant neuronal damage can occur if the percentage of mtDNA mutations may reach a critical threshold. mtDNA mutations also accumulate during normal aging. Here we quantified the 5 kB common mtDNA deletion (CD) using real-time PCR in various brain regions from neurodegenerative disorders and controls. We confirmed previous results that the CD levels increase with age, reaching highest levels in the basal ganglia. High CD levels were also found in affected regions in frontotemporal dementia, Parkinson's disease, and dementia with Lewy bodies, but not in Alzheimer's disease. This suggests that mtDNA damage may occur in a region-specific distribution in neurodegenerative disorders.

摘要

线粒体DNA（mtDNA）畸变引起的线粒体功能障碍与神经退行性疾病中的神经元死亡有关。如果mtDNA突变的百分比达到临界阈值，就可能发生显著的神经元损伤。mtDNA突变也会在正常衰老过程中积累。在这里，我们使用实时PCR对神经退行性疾病患者和对照组的不同脑区中5千碱基对的常见mtDNA缺失（CD）进行了定量分析。我们证实了之前的结果，即CD水平随年龄增长而增加，在基底神经节中达到最高水平。在额颞叶痴呆、帕金森病和路易体痴呆的受累区域也发现了高CD水平，但在阿尔茨海默病中未发现。这表明在神经退行性疾病中，mtDNA损伤可能以区域特异性分布的方式发生。