Deficiency of the Mre11 DNA repair complex in Alzheimer's disease brains
Deficiency of the Mre11 DNA repair complex in Alzheimer's disease brains
复制标题
DOI：
10.1016/j.molbrainres.2004.05.023
复制
发表时间：
2004-09-10
期刊：
影响因子：
--
通讯作者：
Chang, Y
中科院分区：
文献类型：
--
作者：
Jacobsen, E;Beach, T;Chang, Y
阿尔茨海默病（AD）脑的标志是Abeta斑块的沉积、神经元缠结的出现和神经元细胞的广泛损失。虽然Abeta斑块和神经元缠结在神经元的致病性功能障碍中起重要作用，但加速神经退行性过程的因素仍有待确定。本研究中检查的一组因素是Mre 1 I蛋白复合物，由Rad 50、Mre I和Nbs 1组成。这种蛋白质复合物在细胞对DNA损伤的反应中起着至关重要的作用，例如启动细胞周期检查点和修复受损的DNA。这种蛋白质复合物的任何组分的缺陷都对细胞有害。最近，一些研究小组已经观察到AD神经元中的异常细胞周期调节和/或累积的DNA损伤。这些病理改变可能是由Mrel 1复合体中的任何妥协引起或加剧的。在这项研究中，我们比较了来自AD和年龄匹配的非痴呆对照组的脑样本中Mre II I复合蛋白的水平。我们首次表明，MRE II I复合蛋白存在于成年人大脑皮层和小脑的神经元中。这些蛋白质被发现在AD皮层神经元中显著减少。我们的研究结果表明，Mre I I复合物的损失可能与AD的发病机制。(C)2004 Elsevier B. V.保留所有权利。
The hallmarks of Alzheimer's disease (AD) brains are deposition of Abeta plaques, appearance of neurofibrillary tangles, and extensive loss of neuronal cells. While Abeta plaques and neurofibrillary tangles play a significant role in the pathogenic dysfunction of neurons, factors that accelerate the neurodegenerating process remain to be defined. One set of factors examined in this study is the Mre1 I protein complex, composed of Rad50, Mre I I and Nbs1. This protein complex plays an essential role in cellular responses to DNA damage, such as initiating cell cycle checkpoints and repairing damaged DNA. A defect in any component of this protein complex is detrimental to cells. Recently, several groups have observed abnormal cell cycle regulation and/or accumulated DNA damage in AD neurons. These pathological alterations could conceivably be caused or exacerbated by any compromise in the Mrel1 complex. In this study, we compared the levels of the Mre I I complex proteins in brain samples from AD and age-matched non-dementia controls. We show for the first time that the Mre I I complex proteins are present in neurons of the adult human cortex and cerebellum. These proteins were found substantially reduced in the neurons of AD cortex. Our finding suggests that the loss of the Mre I I complex may be associated with the pathogenesis of AD. (C) 2004 Elsevier B.V. All rights reserved.