[Neuronal death: potential role of the nuclear enzyme, poly (ADP-ribose) polymerase].
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.
Boulu
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Université René Descartes-Faculté des Sciences Pharmaceutiques et Biologiques-4, avenue de l'Observatoire-75270 Paris.
Mesenge
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Charriaut-Marlangue
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Verrecchia
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Plotkine
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D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001549:Benzamides / Q000627:therapeutic use; D002545:Brain Ischemia / Q000188:drug therapy / Q000201:enzymology*; D004249:DNA Damage / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D017353:Gene Deletion; D006801:Humans; D051379:Mice; D009474:Neurons / Q000502:physiology*; D018696:Neuroprotective Agents / Q000627:therapeutic use; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000737:chemistry / Q000502:physiology*; D051381:Rats
D001549:Benzamides; D018696:Neuroprotective Agents; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; C025160:3-aminobenzamide; D011065:Poly(ADP-ribose) Polymerases