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Trends Pharmacol Sci. 1999 Apr;20(4):171-81.

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

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1
Department of Neuroscience, The Johns Hopkins University, School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205, USA.

Abstract

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.

PMID:
10322503
[Indexed for MEDLINE]
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