Boulu R G, Mesenge C, Charriaut-Marlangue C, Verrecchia C, Plotkine M
Université René Descartes-Faculté des Sciences Pharmaceutiques et Biologiques-4, avenue de l'Observatoire-75270 Paris.
Bull Acad Natl Med. 2001;185(3):555-63; discussion 564-5.
Poly(ADP-ribose) polymerase (PARP, EC 2.4.2.30) is known as a nuclear enzyme that is activated by DNA strand breaks to participate in DNA repair. It is also called poly(ADP-ribose) synthase (PARS) or poly(ADP-ribose) transferase (PADRT). In physiological conditions, PARP plays an important role in maintaining genomic stability. However, for several pathological situations, which include massive DNA injury (brain ischemia for example), excessive activation of PARP can deplete stores of nicotinamide adenine dinucleotide (NAD+), the PARP substrate, which, with the subsequent ATP depletion, leads to cell death. PARP activation appears to play a major role in neuronal death induced by cerebral ischemia, traumatic brain injury, Parkinson disease and other pathologies. PARP inhibitors (3-aminobenzamide and other compounds) and PARP gene deletion induced dramatic neuroprotection in experimental animals (rats, mice). Accordingly, these data suggest that PARP inhibitors could provide a novel therapeutic approach in a wide range of neurodegenerative disorders including cerebral ischemia and traumatic brain injury.
聚（ADP - 核糖）聚合酶（PARP，EC 2.4.2.30）是一种核酶，可被DNA链断裂激活以参与DNA修复。它也被称为聚（ADP - 核糖）合酶（PARS）或聚（ADP - 核糖）转移酶（PADRT）。在生理条件下，PARP在维持基因组稳定性方面发挥重要作用。然而，在几种病理情况下，包括大量DNA损伤（例如脑缺血），PARP的过度激活会耗尽烟酰胺腺嘌呤二核苷酸（NAD +）的储存，NAD +是PARP的底物，随后ATP耗尽会导致细胞死亡。PARP激活似乎在脑缺血、创伤性脑损伤、帕金森病和其他病理引起的神经元死亡中起主要作用。PARP抑制剂（3 - 氨基苯甲酰胺和其他化合物）以及PARP基因缺失在实验动物（大鼠、小鼠）中诱导了显著的神经保护作用。因此，这些数据表明PARP抑制剂可以为包括脑缺血和创伤性脑损伤在内的多种神经退行性疾病提供一种新的治疗方法。
