Nagy Z, Esiri M M, Smith A D
Oxford Project To Investigate Memory and Ageing, Department of Neuropathology, University of Oxford, UK.
Neuroscience. 1998 Dec;87(4):731-9. doi: 10.1016/s0306-4522(98)00293-0.
Evidence is growing of a role of apoptosis in neurodegenerative disorders including Alzheimer's disease. Recent research indicates that cell cycle disturbances may promote apoptosis in neurodegenerative diseases. In this commentary we will discuss the control of the cell cycle in mammalian cells in general and in the central nervous system in particular. We then summarize the evidence for cell cycle perturbations in Alzheimer's disease and discuss the possible significance these may have for the development of pathological changes in this disease. Our working hypothesis is that, contrary to previous belief, neurons in the adult human brain are capable of re-entering the cell division cycle. The progression of the cell cycle is normally arrested at an early stage and neurons are able to re-differentiate. However, in Alzheimer's disease the cell cycle is allowed to progress into the G2 phase. At this stage re-differentiation is not possible and the neurons will suffer one of two fates: either they will die via an apoptotic pathway or they may produce Alzheimer-type pathology.
细胞凋亡在包括阿尔茨海默病在内的神经退行性疾病中的作用，相关证据正在不断增加。最近的研究表明，细胞周期紊乱可能会促进神经退行性疾病中的细胞凋亡。在这篇评论中，我们将总体讨论哺乳动物细胞中，尤其是中枢神经系统中细胞周期的调控。然后，我们总结阿尔茨海默病中细胞周期紊乱的证据，并讨论这些紊乱可能对该疾病病理变化发展具有的潜在意义。我们的工作假设是，与之前的看法相反，成人大脑中的神经元能够重新进入细胞分裂周期。细胞周期的进程通常在早期就被阻断，神经元能够重新分化。然而，在阿尔茨海默病中，细胞周期会进入G2期。在此阶段，重新分化已不可能，神经元将面临两种命运之一：要么通过凋亡途径死亡，要么可能产生阿尔茨海默病类型的病理变化。
