Poly (ADP-ribose) polymerase, nitric oxide and cell death

Andrew A. Pieper, Ajay Verma, Jie Zhang, Solomon H. Snyder

Research output: Contribution to journalReview articlepeer-review

456 Scopus citations


Poly (ADP-ribose) polymerase (PARP) is a nuclear enzyme that is activated by DNA strand breaks to participate in DNA repair. Excessive activation of PARP, however, can deplete tissue stores of nicotinamide adenine dinucleotide (NAD), the PARP substrate which, with the resultant depletion of ATP, leads to cell death. In many cases of CNS damage, for example vascular stroke, nitric oxide release is a key stimulus to DNA damage and PARP activation. In conditions as diverse as focal cerebral ischaemia, myocardial infarction and toxin-induced diabetes, PARP inhibitors and PARP gene deletion afford dramatic protection from tissue damage. Accordingly, PARP inhibitors could provide novel therapeutic approaches in a wide range of clinical disorders.

Original languageEnglish (US)
Pages (from-to)171-181
Number of pages11
JournalTrends in Pharmacological Sciences
Issue number4
StatePublished - Apr 1 1999

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology


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