Poly(ADP-ribose) polymerase and the therapeutic effects of its inhibitors

Poly(ADP-ribose) polymerases (PARPs) are involved a number of cellular processes, including DNA repair, the regulation of transcription, apoptosis and necrosis.PARP activation initiates an energy-consuming inefficient cellular metabolic cycle; this leads to cellular and mitochondrial dysfunction, and promotes the functional impairment of the affected cells, which culminates in cell necrosis.PARP activation is involved in a range of disorders, including various forms of reperfusion injury, inflammation and cardiovascular diseases. PARP inhibitors have been tested in disease models for these conditions, and also investigated for their ability to suppress DNA repair and to promote apoptosis in cells that are treated with certain anticancer agents.Many classes of compounds have been shown to inhibit the catalytic activity of PARP. Moreover, some of these compounds have now successfully progressed through the preclinical efficacy and safety stages of drug development, and have entered human clinical testing.