背景 多聚ADP核糖聚合酶-1(Poly ADP-ribose polymerase-1,PARP-1)作为一种DNA修复酶，具有维持基因组稳定的生理作用，应激条件下介导细胞程序性死亡，即PARP-1依赖性细胞死亡（PARthanatos）。目的 研究PARP-1及其介导的细胞死亡在脑卒中和神经退行性疾病等神经系统疾病中作用，探讨PARP-1阻断对神经细胞的保护作用。内容 持续氧化应激可使PARP-1过度活化，促进凋亡诱导因子（apoptosis induced factor, AIF）转位至细胞核，介导PARthanatos。缺血再灌注以及谷氨酸兴奋性毒性作用均可产生大量氧自由基，是神经系统疾病主要致病物质。脑卒中和神经退行性疾病中存在持续氧化应激和PARP-1活化，其介导的PARthanatos是神经元死亡的主要方式之一。抑制PARP-1活化具有神经保护作用。趋向 PARP-1活化介导脑卒中和神经退行性疾病的发生，阻断PARP-1有望成为治疗该类疾病的新靶点。
Background Poly ADP-ribose polymerase-1(PARP-1), a main DNA repair enzyme, mediates PARthanatos under stress while it maintains genome stability under physiologic status. Objective To investigate the effect of PARP-1 and PARthanatos in the pathogenesis of nervous system diseases and to discuss the therapeutic value of PARP-1 blocking. Content Persistent DNA stress induces hyper-activation of PARP-1 and translocation of apoptosis induced factor (AIF) from mitochondria into nucleus, followed with chromosome condensation, which is characteristics of PARthanatos. Ischemic reperfusion in strokes produces robust reactive oxygen species (ROS) while glutamate and other substances trigger release of superoxide and ROS which mediate neurodegenerative diseases. Sustained activation of PARP-1 and PARthanatos through oxidative stress is involved in these diseases and its inhibition had significant alleviation of neuron death. Trend Hyper activation of PARP-1 triggers pathologic changes in stroke and neurodegenerative diseases. PARP-1 blockade may be a new strategy to promote neuron survival in stroke and neurodegenerative diseases.
Cited
)
