DNA damage in neurodegenerative diseases
DNA damage in neurodegenerative diseases
复制标题
DOI：
10.1016/j.mrfmmm.2014.11.010
复制
发表时间：
2015-06-01
影响因子：
2.3
通讯作者：
Migliore, Lucia
中科院分区：
文献类型：
--
作者：
Coppede, Fabio;Migliore, Lucia
在观察到从受神经变性疾病影响的患者的死后脑区域提取的核和线粒体DNA中的氧化性DNA损伤增加之后，上个世纪的最后几年和本世纪的前十年主要致力于在神经再生的早期、中期或晚期阶段的患者的神经元样品和外周组织中寻找DNA损伤的标记物。这些研究证明了氧化性DNA损伤是神经变性中最早可检测的事件之一，但也揭示了神经变性病症中的细胞遗传学损伤，例如阿尔茨海默病中21号染色体分离不良的趋势。正如许多神经退行性疾病的危险因素所发生的那样，DNA损伤是神经退行性疾病过程的原因还是结果的问题仍然是开放的，可能两者都是正确的。近年来，随着越来越多的证据表明表观遗传机制对学习、记忆过程、行为障碍和神经退行性疾病有重大贡献，氧化应激标志物的研究兴趣转向寻找神经退行性疾病的表观遗传生物标志物。然而，越来越多的证据将DNA损伤和修复与表观遗传现象联系起来，从而为神经退行性疾病中一个非常有吸引力和及时的研究课题开辟了道路。我们将在阿尔茨海默病，帕金森病和肌萎缩侧索硬化症的背景下解决这些问题，这是人类最常见的三种神经退行性病变。(C)2014爱思唯尔有限公司版权所有。
Following the observation of increased oxidative DNA damage in nuclear and mitochondrial DNA extracted from post-mortem brain regions of patients affected by neurodegenerative diseases, the last years of the previous century and the first decade of the present one have been largely dedicated to the search of markers of DNA damage in neuronal samples and peripheral tissues of patients in early, intermediate or late stages of neuroclegeneration. Those studies allowed to demonstrate that oxidative DNA damage is one of the earliest detectable events in neurodegeneration, but also revealed cytogenetic damage in neurodegenerative conditions, such as for example a tendency towards chromosome 21 malsegregation in Alzheimer's disease. As it happens for many neurodegenerative risk factors the question of whether DNA damage is cause or consequence of the neurodegenerative process is still open, and probably both is true. The research interest in markers of oxidative stress was shifted, in recent years, towards the search of epigenetic biomarkers of neurodegenerative disorders, following the accumulating evidence of a substantial contribution of epigenetic mechanisms to learning, memory processes, behavioural disorders and neurodegeneration. Increasing evidence is however linking DNA damage and repair with epigenetic phenomena, thereby opening the way to a very attractive and timely research topic in neurodegenerative diseases. We will address those issues in the context of Alzheimer's disease, Parkinson's disease, and Amyotrophic Lateral Sclerosis, which represent three of the most common neurodegenerative pathologies in humans. (C) 2014 Elsevier B.V. All rights reserved.