Poly(ADP-ribose) polymerase-1 (PARP-1) and its therapeutic implications

Abstract Poly(ADP-ribose) polymerases (PARPs) are a family of cell signaling enzymes present in eukaryotes, which are involved in the poly(ADP-ribosylation) of DNA binding proteins. While an 18 member superfamily of PARPs has been identified, however PARP-1 the most abundant isoform accounts for mor...

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Bibliographic Details
Published in:Vascular pharmacology 2010-09, Vol.53 (3), p.77-87
Main Authors: Sodhi, Rupinder K, Singh, Nirmal, Jaggi, Amteshwar S
Format: Article
Language:English
Subjects:
Aging - metabolism
Animals
Apoptosis
Cardiovascular
Diabetes Mellitus - drug therapy
Diabetes Mellitus - enzymology
DNA Repair
HIV Infections - drug therapy
HIV Infections - enzymology
Humans
Inflammation - enzymology
Molecular Targeted Therapy
Necrosis
Neoplasms - drug therapy
Neoplasms - enzymology
PARP inhibitors
PARP-1
Poly(ADP-ribose) Polymerase Inhibitors
Poly(ADP-ribose) Polymerases - physiology
Reperfusion Injury - drug therapy
Reperfusion Injury - enzymology
Signal Transduction
Zinc Fingers
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Summary:Abstract Poly(ADP-ribose) polymerases (PARPs) are a family of cell signaling enzymes present in eukaryotes, which are involved in the poly(ADP-ribosylation) of DNA binding proteins. While an 18 member superfamily of PARPs has been identified, however PARP-1 the most abundant isoform accounts for more than 90% of its functions. PARP-1 works as DNA damage nick sensor, which uses NAD+ to form polymers of ADP-ribose (PAR) and nicotinamide. Three consequences of the activation of PARP-1 are particularly important for drug development: first, its role in DNA repair; second, its capacity to deplete cellular energetic pools, which culminates in cell dysfunction and necrosis; and third, its capacity to promote the transcription of proinflammatory genes. Consequently, pharmacological inhibition of PARP has the potential to enhance the cytotoxicity of certain DNA-damaging anticancer drugs, reduce cell necrosis (for example, in stroke or myocardial infarction) and downregulate multiple simultaneous pathways of inflammation and tissue injury (for example, in circulatory shock, colitis or diabetic complications). Through this article we have tried to develop a brief and simplified picture of the principal physiological and pathophysiological roles governed by PARP-1 and its therapeutic implications.
ISSN:1537-1891
1879-3649
DOI:10.1016/j.vph.2010.06.003