Journal
NEUROBIOLOGY OF DISEASE
Volume 7, Issue 4, Pages 225-239Publisher
ACADEMIC PRESS INC
DOI: 10.1006/nbdi.2000.0324
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Funding
- NIDA NIH HHS [DA00074, DA00266] Funding Source: Medline
- NIMH NIH HHS [MH18501] Funding Source: Medline
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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. (C) 2000 Academic Press.
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