Evidence for the progression through S-phase in the ectopic cell cycle re-entry of neurons in Alzheimer disease.
Evidence for the progression through S-phase in the ectopic cell cycle re-entry of neurons in Alzheimer disease.
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DOI：
10.18632/aging.100044
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发表时间：
2009-04
期刊：
影响因子：
--
通讯作者：
Lee HG
中科院分区：
文献类型：
--
作者：
Bonda DJ;Evans TA;Santocanale C;Llosá JC;Viña J;Bajic V;Castellani RJ;Siedlak SL;Perry G;Smith MA;Lee HG
异常神经元重新进入细胞周期是阿尔茨海默病（AD）的一种潜在病理机制。然而，虽然细胞周期蛋白、细胞周期蛋白依赖激酶（CDKs）和其他有丝分裂因子在神经元中异位表达，但这些蛋白中的许多也参与其他病理和生理过程，这引发了关于这些标记物是否真正指示真正的细胞周期过程的持续争论。为了解决这个问题，我们分析了一种在DNA复制中起作用的小染色体维持（Mcm）蛋白，它在DNA合成过程中被s期促进CDKs和Cdc7磷酸化。我们发现磷酸化的Mcm2 （pMcm2）与阿尔茨海默氏症患者的神经原纤维缠结、神经丝和营养不良的神经突明显相关，但在年龄匹配的对照组中没有。这些数据不仅为阿尔茨海默病的细胞周期异常提供了进一步的证据，而且pMcm2的细胞质定位而不是核定位表明，阿尔茨海默病中这一重要复制因子的异常细胞分布可能解释了由此导致的细胞周期停滞和随后的神经元变性。
Aberrant neuronal re-entry into the cell cycle is emerging as a potential pathological mechanism in Alzheimer disease (AD). However, while cyclins, cyclin dependent kinases (CDKs), and other mitotic factors are ectopically expressed in neurons, many of these proteins are also involved in other pathological and physiological processes, generating continued debate on whether such markers are truly indicative of a bona fide cell cycle process. To address this issue, here we analyzed one of the minichromosome maintenance (Mcm) proteins that plays a role in DNA replication and becomes phosphorylated by the S-phase promoting CDKs and Cdc7 during DNA synthesis. We found phosphorylated Mcm2 (pMcm2) markedly associated with neurofibrillary tangles, neuropil threads, and dystrophic neurites in AD but not in aged-matched controls. These data not only provide further evidence for cell cycle aberrations in AD, but the cytoplasmic, rather than nuclear, localization of pMcm2 suggests an abnormal cellular distribution of this important replication factor in AD that may explain resultant cell cycle stasis and consequent neuronal degeneration.
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影响因子：
82.9
作者：
Alonso, AD;GrundkeIqbal, I;Iqbal, K
通讯作者：
Iqbal, K
DOI：
10.1093/jnen/61.8.678
发表时间：
2002-08-01
影响因子：
3.2
作者：
Hoozemans, JJM;Brückner, MK;Arendt, T
通讯作者：
Arendt, T
DOI：
10.1164/ajrccm.164.supplement_2.2106069
发表时间：
2001-11-15
影响因子：
24.7
作者：
Clement, A;Henrion-Caude, A;Corroyer, S
通讯作者：
Corroyer, S
影响因子：
5.4
作者：
Kudoh, Ayumi;Daikoku, Tohru;Tsurumi, Tatsuya
通讯作者：
Tsurumi, Tatsuya
影响因子：
78.5
作者：
Gonzalez, MA;Tachibana, KK;Coleman, N
通讯作者：
Coleman, N