McShea A, Wahl A F, Smith M A
Bristol-Myers Squibb, Pharmaceutical Research Institute, Seattle, Washington, USA.
Med Hypotheses. 1999 Jun;52(6):525-7. doi: 10.1054/mehy.1997.0680.
Several recent findings demonstrated increased expression of cell cycle-related proteins in the degenerating neurons found in Alzheimer disease. We hypothesize that this apparent attempt to re-enter the cell cycle is a neuronal response to external growth stimuli that leads to an abortive re-entry into the cell cycle. However, since neurons of adults apparently lack the capacity both to divide in vivo and in vitro, it is possible that they lack the components necessary to complete the cell division process. Nonetheless, the importance of these findings is that they provide an explanation for the increased phosphorylation of cytoskeletal proteins such as tau and neurofilaments that represent the most striking intracellular changes in the disease. Further, it is our contention that inappropriate reentry into the cell cycle and interrupted mitotic processes are significant factors not only in the cytoskeletal pathology but also in the neuronal degeneration that characterizes the pathology of Alzheimer disease.
最近的几项研究结果表明，在阿尔茨海默病中发现的退化神经元中，细胞周期相关蛋白的表达增加。我们假设，这种明显的重新进入细胞周期的尝试是神经元对外部生长刺激的一种反应，导致了进入细胞周期的失败。然而，由于成年神经元显然缺乏在体内和体外分裂的能力，它们可能缺乏完成细胞分裂过程所需的成分。尽管如此，这些发现的重要性在于，它们为细胞骨架蛋白（如tau蛋白和神经丝蛋白）磷酸化增加提供了解释，而这些蛋白的磷酸化增加是该疾病最显著的细胞内变化。此外，我们认为，不适当的重新进入细胞周期和有丝分裂过程的中断不仅是细胞骨架病理学的重要因素，也是阿尔茨海默病病理学特征的神经元退化的重要因素。
