Journal
TRENDS IN PHARMACOLOGICAL SCIENCES
Volume 27, Issue 12, Pages 626-630Publisher
ELSEVIER SCIENCE LONDON
DOI: 10.1016/j.tips.2006.10.003
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Funding
- Intramural NIH HHS [Z01 AA000375-02] Funding Source: Medline
- NIGMS NIH HHS [R01 GM060915-01, R01 GM060915] Funding Source: Medline
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The nuclear enzyme poly(ADP-ribose) polymerase (PARP)-1 has an important role in regulating cell death and cellular responses to DNA repair. Pharmacological inhibitors of PARP have entered clinical testing as cytoprotective agents in cardiovascular diseases and as adjunct antitumor therapeutics. Initially, it was assumed that the regulation of PARP occurs primarily at the level of DNA breakage: recognition of DNA breaks was considered to be the primary regulator (activator) or the catalytic activity of PARK Recent studies have provided evidence that PARP-1 activity can also be modulated by several endogenous factors, including various kinases, purines and caffeine metabolites. There is a gender difference in the contribution of PARP-1 to stroke and inflammatory responses, which is due, at least in part, to endogenous estrogen levels. Several tetracycline antibiotics are also potent PARP-1 inhibitors. In this article, we present an overview of novel PARP-1 modulators.
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