PARP inhibitors: New tools to protect from inflammation

被引：68

作者：

Giansanti, Vincenzo ^{[1
]}

Dona, Francesca ^{[1
]}

Tillhon, Micol ^{[1
]}

Scovassi, A. Ivana ^{[1
]}

机构：

[1] CNR, Ist Genet Mol, I-27100 Pavia, Italy

来源：

BIOCHEMICAL PHARMACOLOGY | 2010年 / 80卷 / 12期

关键词：

Inflammation; Necrosis; NF-kappa B; PARP; ROS; ADP-RIBOSE POLYMERASE; NF-KAPPA-B; SIGNAL-TRANSDUCTION PATHWAYS; DEPENDENT GENE-EXPRESSION; FOCAL CEREBRAL-ISCHEMIA; BASE EXCISION-REPAIR; E-DEFICIENT MICE; POLY(ADP-RIBOSE) POLYMERASE; DNA-REPAIR; GLYCOHYDROLASE PARG;

D O I：

10.1016/j.bcp.2010.04.022

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Poly(ADP-ribosylation) consists in the conversion of beta-NAD(+) into ADP-ribose, which is then bound to acceptor proteins and further used to form polymers of variable length and structure. The correct turnover of poly(ADP-ribose) is ensured by the concerted action of poly(ADP-ribose) polymerase (PARP) and poly(ADP-ribose) glycohydrolase (PARG) enzymes, which are responsible for polymer synthesis and degradation, respectively. Despite the positive role of poly(ADP-ribosylation) in sensing and repairing DNA damage, generated also by ROS, PARP over-activation could allow NAD depletion and consequent necrosis, thus leading to an inflammatory condition in many diseases. In this respect, inhibition of PARP enzymes could exert a protective role towards a number of pathological conditions; i.e. the combined treatment of tumors with PARP inhibitors/anticancer agents proved to have a beneficial effect in cancer therapy. Thus, pharmacological inactivation of poly(ADP-ribosylation) could represent a novel therapeutic strategy to limit cellular injury and to attenuate the inflammatory processes that characterize many disorders. (C) 2010 Elsevier Inc. All rights reserved.

引用

页码：1869 / 1877

页数：9

共 163 条

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