Cell cycle re-entry mediated neurodegeneration and its treatment role in the pathogenesis of Alzheimer's disease.
Cell cycle re-entry mediated neurodegeneration and its treatment role in the pathogenesis of Alzheimer's disease.
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DOI：
10.1016/j.neuint.2008.10.013
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发表时间：
2009-02
影响因子：
4.2
通讯作者：
Smith MA
中科院分区：
文献类型：
--
作者：
Lee HG;Casadesus G;Zhu X;Castellani RJ;McShea A;Perry G;Petersen RB;Bajic V;Smith MA
作为阿尔茨海默病（Alzheimer's disease，AD）最早期的病理改变之一，许多细胞周期相关蛋白的异常再表达和特定脆弱神经元群体中细胞周期调控不当是导致AD和其他神经退行性疾病发病机制的重要组成部分。这些事件清楚地代表了真正的细胞周期，而不是其他过程的副现象，因为在AD和其他神经退行性疾病中，存在导致DNA复制的真正的有丝分裂改变。虽然细胞周期重新进入的确切作用尚不清楚，但最近使用细胞培养和动物模型的研究强烈支持神经元中细胞周期失调导致AD相关病理学发展的观点，如tau蛋白过度磷酸化和淀粉样蛋白-β沉积，并最终导致神经元细胞死亡。重要的是，细胞周期重新进入在突变淀粉样蛋白前体和tau转基因小鼠中也是明显的，并且如在人类疾病中一样，发生在病理学标志、神经细胞缠结和淀粉样蛋白斑块的发展之前。因此，在模型细胞和动物系统中研究异常细胞周期调控可能为AD的发病机制提供极其重要的见解，同时作为测试新的治疗方法的手段。
As one of the earliest pathologic changes, the aberrant re-expression of many cell cycle -related proteins and inappropriate cell cycle control in specific vulnerable neuronal populations in Alzheimer’s disease (AD) is emerging as an important component in the pathogenesis leading to AD and other neurodegenerative diseases. These events are clearly representative of a true cell cycle, rather than epiphenomena of other processes since, in AD and other neurodegenerative diseases, there is a true mitotic alteration that leads to DNA replication. While the exact role of cell cycle re-entry is unclear, recent studies using cell culture and animal models strongly support the notion that the dysregulation of cell cycle in neurons leads to the development of AD-related pathology such as hyperphosphorylation of tau and amyloid-β deposition and ultimately causes neuronal cell death. Importantly, cell cycle re-entry is also evident in mutant amyloid-β protein precursor and tau transgenic mice and, as in human disease, occurs prior to the development of the pathological hallmarks, neurofibrillary tangles and amyloid-β plaques. Therefore, the study of aberrant cell cycle regulation in model cellular and animal systems may provide extremely important insights into the pathogenesis of AD while serving as a means to test novel therapeutic approaches.
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DOI：
10.1073/pnas.0611671104
发表时间：
2007-02-27
影响因子：
11.1
作者：
Hoeglinger, Guenter U.;Breunig, Joshua J.;Hunot, Stephane
通讯作者：
Hunot, Stephane
DOI：
10.1083/jcb.139.2.485
发表时间：
1997-10-20
期刊：
The Journal of cell biology
影响因子：
--
作者：
Janicki S;Monteiro MJ
通讯作者：
Monteiro MJ
影响因子：
82.9
作者：
Alonso, AD;GrundkeIqbal, I;Iqbal, K
通讯作者：
Iqbal, K
影响因子：
1.6
作者：
Barni, S;Sciola, L;Pippia, P
通讯作者：
Pippia, P
DOI：
10.1073/pnas.89.4.1194
发表时间：
1992-02-15
影响因子：
11.1
作者：
ALUBAIDI, MR;HOLLYFIELD, JG;BAEHR, W
通讯作者：
BAEHR, W