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

Hyo Chol Ha, Solomon H. Snyder

Research output: Contribution to journalReview articlepeer-review

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 languageEnglish (US)
Pages (from-to)225-239
Number of pages15
JournalNeurobiology of Disease
Volume7
Issue number4
DOIs
StatePublished - 2000

ASJC Scopus subject areas

  • Neurology

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