Copani Agata, Caraci Filippo, Hoozemans Jeroen J M, Calafiore Marco, Sortino Maria Angela, Nicoletti Ferdinando
Department of Pharmaceutical Sciences, University of Catania, Italy.
Biochim Biophys Acta. 2007 Apr;1772(4):409-12. doi: 10.1016/j.bbadis.2006.10.016. Epub 2006 Nov 1.
The mechanism whereby a reactivation of cell cycle in neurons causes cell death is beginning to be identified. In cellular models of Alzheimer's disease, activation of a non-canonical pathway of DNA replication contributes to neuronal death. This pathway involves the repair enzyme DNA polymerase-beta, which is highly expressed in neurons of the Alzheimer's brain at early stages of the disease. Loading of DNA polymerase-beta into the replication forks generates a death signal, which involves the tumor suppressor p53. The increasing knowledge of the main actors of the unscheduled DNA replication in neurons will pave the way for novel therapeutic interventions in Alzheimer's disease and other neurodegenerative disorders.
神经元中细胞周期重新激活导致细胞死亡的机制正开始被识别。在阿尔茨海默病的细胞模型中，非经典DNA复制途径的激活促成神经元死亡。该途径涉及修复酶DNA聚合酶β，其在疾病早期的阿尔茨海默病大脑神经元中高度表达。将DNA聚合酶β加载到复制叉中会产生一个死亡信号，其中涉及肿瘤抑制因子p53。对神经元中异常DNA复制主要参与者的了解不断增加，将为阿尔茨海默病和其他神经退行性疾病的新型治疗干预铺平道路。
