PARP inhibitors: new tools to protect from inflammation.

Abstract:

:Poly(ADP-ribosylation) consists in the conversion of β-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.

journal_name

Biochem Pharmacol

journal_title

Biochemical pharmacology

authors

Giansanti V,Donà F,Tillhon M,Scovassi AI

doi

10.1016/j.bcp.2010.04.022

subject

Has Abstract

pub_date

2010-12-15 00:00:00

pages

1869-77

issue

12

eissn

0006-2952

issn

1873-2968

pii

S0006-2952(10)00296-0

journal_volume

80

pub_type

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