Poly(ADP-ribose) polymerase-1 in the nervous system.
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.
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Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205, USA.
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D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D016923:Cell Death / Q000502:physiology; D006801:Humans; D009243:NAD / Q000378:metabolism*; D009336:Necrosis; D009424:Nervous System Physiological Phenomena; D009474:Neurons / Q000502:physiology*; D011065:Poly(ADP-ribose) Polymerases / Q000502:physiology*
D009243:NAD; D000255:Adenosine Triphosphate; D011065:Poly(ADP-ribose) Polymerases