Review: cell cycle aberrations and neurodegeneration.

Review: cell cycle aberrations and neurodegeneration.
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DOI:
10.1111/j.1365-2990.2010.01064.x
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发表时间:
2010-04
影响因子:
5
通讯作者:
Lee HG
Lee HG
中科院分区:
医学2区
文献类型:
--
作者:
Bonda DJ;Bajić VP;Spremo-Potparevic B;Casadesus G;Zhu X;Smith MA;Lee HG

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细胞周期是一个高度调控和基本的细胞过程,涉及许多蛋白质的复杂反馈调节,任何对其完整性的妥协都会导致细胞的可怕后果。例如,在阿尔茨海默病(AD)等神经退行性疾病中,异常细胞周期再进入的证据先于其他疾病的标志,因此,在AD的病因学中暗示了细胞周期畸变。然而,阿尔茨海默病细胞周期再进入的机制尚不清楚。目前的理论表明,它是早期事件组合的一部分,这些事件共同引发了与该疾病一致的退行性病理和认知表型。我们提出了一个“双重打击假说”,强调细胞周期改变和氧化应激之间的协调相互作用,共同产生神经变性。在这里,我们回顾了有关AD中细胞周期机制的证据,以及这些变化,特别是与氧化应激结合时,如何导致一系列导致疾病的事件。基于这一概念,我们提出了疾病治疗的新机遇。
The cell cycle is a highly regulated and fundamental cellular process that involves complex feedback regulation of many proteins, and any compromise to its integrity elicits dire consequences for the cell. For example, in neurodegenerative diseases such as Alzheimer disease (AD), evidence for abnormal cell cycle re-entry precedes other hallmarks of disease and as such, implicates cell cycle aberrations in the aetiology of AD. The mechanism(s) for cell cycle re-entry in AD, however, remain unclear. Current theory suggests it to be part of a combination of early events that together elicit the degenerative pathology and cognitive phenotype consistent with the disease. We propose a ‘Two-Hit Hypothesis’ that highlights the concerted interaction between cell cycle alterations and oxidative stress that combine to produce neurodegeneration. Here, we review the evidence implicating cell cycle mechanisms in AD and how such changes, especially in combination with oxidative stress, would lead to a cascade of events leading to disease. Based on this concept, we propose new opportunities for disease treatment.
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