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Neurobiol Dis. 2000 Aug;7(4):225-39.

Poly(ADP-ribose) polymerase-1 in the nervous system.

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Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205, USA.


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.

[Indexed for MEDLINE]

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