Poly(ADP-ribose) polymerase, its potential role in neuronal death

Poly(ADP-ribose) polymerase (PARP, EC 2.4.2.30) is known,l as a nuclear enz yme that is activated by DNA str and breaks to participate in DNA repair: I t is also called poly (ADP-ribose) synthase (PARS) ol poly(ADP-ribose) tran sferase (PADRT). In physiological conditions PARP plays an important, role in maintaining genomic stability However; in sever al pathological situatio ns, which include massive DNA injury (brain ischemia for example), excessiv e activation of PARP call deplete stores of nicotinamide adenine dinucleoti de (NAD(+)), the PARP substrate, which, with the subsequent ATP depletion, leans to cell death. PARP activation appears to play a major role in neuron al death included by cerebral ischemia, traumatic blain injury Parkinson di sease and other pathologies. PARP inhibitors (3-aminobenzamide and other co mpounds) and PARP gene deletion induced dramatic neuroprotection in experim ental animals (rats, mice). Accordingly these data suggest that PARP inhibi tors could provide a novel therapeutic approach in a wide range of neurodeg enerative disorders including cerebral ischemia and traumatic brain injury.