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.