TY - JOUR
T1 - Novel modulators of poly(ADP-ribose) polymerase
AU - Szabo, Csaba
AU - Pacher, Pal
AU - Swanson, Raymond A.
N1 - Funding Information:
This work was supported in part by the Intramural Research Program of the National Institutes of Health and National Institute on Alcohol Abuse and Alcoholism (to P.P.) and by grant R01 from the National Institutes of Health (to C.S. and R.S.).
Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2006/12
Y1 - 2006/12
N2 - 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 PARP. 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.
AB - 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 PARP. 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.
UR - http://www.scopus.com/inward/record.url?scp=33750932728&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33750932728&partnerID=8YFLogxK
U2 - 10.1016/j.tips.2006.10.003
DO - 10.1016/j.tips.2006.10.003
M3 - Article
C2 - 17055069
AN - SCOPUS:33750932728
SN - 0165-6147
VL - 27
SP - 626
EP - 630
JO - Trends in Pharmacological Sciences
JF - Trends in Pharmacological Sciences
IS - 12
ER -