Poly(ADP-ribose) polymerase as a drug target for cardiovascular disease and cancer: An update

Eszter M. Horváth, Csaba Szabo

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

Poly(ADP-ribose) polymerase-1 (PARP-1) is a member of the PARP enzyme family consisting of PARP-1 and four additional, recently identified poly(ADP-ribosylating) enzymes. PARP-1 is one of the most abundant nuclear proteins and functions as a DNA nick sensor enzyme. Upon binding to DNA breaks, activated PARP cleaves NAD+ into nicotinamide and ADP-ribose and polymerizes the latter onto nuclear acceptor proteins including histones, transcription factors and PARP itself. On one hand, PARP is viewed as a guardian angel of genomic integrity, and inhibition of PARP has been used to facilitate the death of tumor cells alone, or in combination with antitumor agents. On the other hand, overactivation of PARP in response to oxidant- and free radical-mediated excessive DNA single strand breaks promotes cell dysfunction and necrotic type cell death in a variety of pathophysiological conditions. Pharmacological inhibition of PARP, consequently, exerts cytoprotective effects in a variety of diseases including stroke, myocardial infarction, heart failure and diabetes mellitus. The research into the role of PARP in diabetic cardiovascular injury is now supported by novel tools such as new classes of potent inhibitors of PARP as well as genetically engineered animals lacking the gene for PARP. In addition, potent PARP inhibitors have entered the stage of clinical testing. The current review provides an update on the most recent developments in the area of PARP.

Original languageEnglish (US)
Pages (from-to)171-181
Number of pages11
JournalDrug News and Perspectives
Volume20
Issue number3
DOIs
StatePublished - Apr 2007
Externally publishedYes

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Poly(ADP-ribose) Polymerases
Single-Stranded DNA Breaks
Cardiovascular Diseases
Nuclear Proteins
Cell Death
Enzymes
Pharmaceutical Preparations
Adenosine Diphosphate Ribose
Neoplasms
Genetically Modified Animals
DNA Breaks
Oxidants
Antineoplastic Agents
NAD
Histones
Adenosine Diphosphate
Free Radicals
Diabetes Mellitus
Transcription Factors
Heart Failure

ASJC Scopus subject areas

  • Pharmacology

Cite this

Poly(ADP-ribose) polymerase as a drug target for cardiovascular disease and cancer : An update. / Horváth, Eszter M.; Szabo, Csaba.

In: Drug News and Perspectives, Vol. 20, No. 3, 04.2007, p. 171-181.

Research output: Contribution to journalArticle

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