Abstract
Although the cell cycle machinery is essentially linked to cellular proliferation, recent findings suggest that neuronal cell death is frequently concurrent with the aberrant expression of cell cycle proteins in post-mitotic neurons. The present work reviews the evidence of cell cycle reentry and expression of cell cycle-associated proteins as a complex response of neurons to insults in the adult brain but also as a mechanism underlying brain plasticity. The basic aspects of cell cycle mechanisms, as well as the evidence showing cell cycle protein expression in the injured brain, are reviewed. The discussion includes recent experimental work attempting to establish a correlation between altered brain plasticity and neuronal death, and an analysis of recent evidence on how neural cell cycle dysregulation is related to neurodegenerative diseases especially the Alzheimer’s disease. Understanding the mechanisms that control reexpression of proteins required for cell cycle progression which is involved in brain remodeling, may shed new light into the mechanisms involved in neuronal demise under diverse pathological circumstances. This would provide valuable clues about the possible therapeutic targets, leading to potential treatment of presently challenging neurodegenerative diseases.
Keywords: Alzheimer’s disease, cell cycle, neurodegeneration, brain plasticity
摘要
细胞周期主要与细胞增殖有关。 最近研究显示, 有丝分裂期后的神经元细胞死亡经常伴随有细胞周期调节蛋白的异常表达。 细胞重新进入细胞周期以及细胞周期相关蛋白的表达是神经元对大脑损伤的应答, 也是大脑可塑性的一种机制。 本文主要就此进行综述, 并对大脑可塑性变化与神经元死亡的联系, 以及神经元细胞周期失调与神经退行性疾病特别是阿尔茨海默病的关系进行了讨论。 了解细胞周期进展过程中必需蛋白质的再表达, 将会帮助揭示不同病理环境下神经元凋亡的机制, 并提示神经退行性疾病的一些潜在治疗靶点。
关键词: 阿尔茨海默病, 细胞周期, 神经退行性病变, 大脑可塑性
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