The X-chromosome instability phenotype in Alzheimer's disease: A clinical sign of accelerating aging?
The X-chromosome instability phenotype in Alzheimer's disease: A clinical sign of accelerating aging?
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DOI：
10.1016/j.mehy.2009.06.046
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发表时间：
2009-12-01
影响因子：
4.7
通讯作者：
Smith, Mark A.
中科院分区：
文献类型：
--
作者：
Bajic, Vladan P.;Spremo-Potparevic, Biljana;Smith, Mark A.
过早的着丝粒分裂，或过早的着丝粒分离（PCS），发生在染色单体分离功能障碍时，在有丝分裂的间期阶段比平常更早发生。在罗伯特综合征和各种癌症中观察到的这种现象也在阿尔茨海默病（AD）的外周和神经元细胞中有记录。在后一种情况下，将荧光原位杂交（FISH）应用于AD患者外周血淋巴细胞间期核中X染色体的着丝粒区域，证明在DNA复制完成后直接在有丝分裂中期之前过早发生染色体分离细胞周期的G（2）期。此外，可能出乎意料地考虑到终末分化神经元的假定有丝分裂后状态，AD患者的神经元也显示X染色体的PCS水平显著增加。与其他现象，如细胞周期再激活和异位再表达的细胞周期蛋白和细胞周期蛋白依赖性蛋白，我们建议，AD是一种致癌表型，导致受影响的大脑加速老化。(C)2009爱思唯尔有限公司保留所有权利。
Premature centromere division, or premature centromere separation (PCS), occurs when chromatid separation is dysfunctional, occurring earlier than usual during the interphase stage of mitosis. This phenomenon, seen in Robert's syndrome and various cancers, has also been documented in peripheral as well as neuronal cells of Alzheimer's disease (AD). In the latter instances, fluorescent in situ hybridization (FISH), applied to the centromere region of the X-chromosome in interphase nuclei of lymphocytes from peripheral blood in AD patients, demonstrated premature chromosomal separation before mitotic metaphase directly after completion of DNA replication in G(2) phase of the cell cycle. Furthermore, and perhaps unexpectedly given the presumptive post-mitotic status of terminally differentiated neurons, neurons in AD patients also showed significantly increased levels of PCS of the X-chromosome. Taken together with other phenomena such as cell cycle re-activation and ectopic re-expression of cyclins and cyclin dependent proteins, we propose that AD is an oncogenic phenotype leading to accelarated aging of the affected brain. (C) 2009 Elsevier Ltd. All rights reserved.