Herrup Karl
Dept. of Cell Biology and Neuroscience, Nelson Biological Laboratories, 604 Allison Road, Piscataway, NJ 0854, USA.
Front Biosci (Elite Ed). 2012 Jan 1;4(6):2101-9. doi: 10.2741/527.
Alzheimer's disease is a neurodegenerative disorder that accounts for the majority of the dementia in individuals over the age of 65. While much has been learned about the biology and biochemistry of the tau tangles and beta-amyloid plaques, less is known about the cell biology of the neuronal cell death process. This review examines one feature of this process, the unexpected occurrence of unscheduled cell cycle events in mature and normally non-mitotic neurons in the at-risk neuronal populations. The correlation of neuronal cell cycling and cell death is not unique to Alzheimer's, but the evidence in both human Alzheimer's disease and its mouse models suggests that these events are early disease related processes, that they are driving forces of the disease rather than indirect symptoms. Defining the biochemistry behind cell cycle initiation holds promise as a fresh therapeutic approach in the battle against this devastating disease.
阿尔茨海默病是一种神经退行性疾病，占65岁以上人群痴呆症的大部分。虽然我们已经对tau缠结和β-淀粉样蛋白斑块的生物学和生物化学有了很多了解，但对于神经元细胞死亡过程的细胞生物学却知之甚少。本综述探讨了这一过程的一个特征，即在有风险的神经元群体中，成熟且通常不进行有丝分裂的神经元意外发生了非计划的细胞周期事件。神经元细胞周期与细胞死亡之间的关联并非阿尔茨海默病所特有，但在人类阿尔茨海默病及其小鼠模型中的证据表明，这些事件是与疾病早期相关的过程，它们是疾病的驱动因素而非间接症状。确定细胞周期启动背后的生物化学机制有望成为对抗这种毁灭性疾病的一种新的治疗方法。
