Abstract
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 district genes and lacking classic DNA-binding domains may have nonnuclear functions, perhaps linked to cellular energy dynamics. (C) 2000 Academic Press.
Original language | English (US) |
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Pages (from-to) | 225-239 |
Number of pages | 15 |
Journal | Neurobiology of Disease |
Volume | 7 |
Issue number | 4 |
DOIs | |
State | Published - 2000 |
ASJC Scopus subject areas
- Neurology