Ha H C, Snyder S H
Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205, USA.
Neurobiol Dis. 2000 Aug;7(4):225-39. doi: 10.1006/nbdi.2000.0324.
Poly(ADP-ribose) polymerase-1 (PARP-1) is a nuclear enzyme, activated by DNA strand breaks to participate in DNA repair. Overactivation of PARP by cellular insults depletes its substrate NAD(+) and then ATP, leading to a major energy deficit and cell death. This mechanism appears to be prominent in vascular stroke and other neurodegenerative processes in which PARP gene deletion and PARP-inhibiting drugs provide major protection. Cell death associated with PARP-1 overactivation appears to be predominantly necrotic while apoptosis is associated with PARP-1 cleavage, which may conserve energy needed for the apoptotic process. Novel forms of PARP derived from distinct genes and lacking classic DNA-binding domains may have nonnuclear functions, perhaps linked to cellular energy dynamics.
聚（ADP - 核糖）聚合酶 -1（PARP -1）是一种核酶，可被DNA链断裂激活以参与DNA修复。细胞损伤导致的PARP过度激活会耗尽其底物烟酰胺腺嘌呤二核苷酸（NAD(+)），进而耗尽三磷酸腺苷（ATP），导致严重的能量缺乏和细胞死亡。这种机制在血管性中风和其他神经退行性过程中似乎很突出，其中PARP基因缺失和PARP抑制药物可提供主要保护作用。与PARP -1过度激活相关的细胞死亡似乎主要是坏死性的，而凋亡则与PARP -1裂解有关，这可能为凋亡过程节省所需能量。源自不同基因且缺乏经典DNA结合域的新型PARP可能具有非核功能，或许与细胞能量动态有关。
