[Poly(ADP-ribose) polymerase (PARP): physiological and pathological roles].

PARPs are a large family of 18 enzymes found in most eukaryotes. PARP-1, the most abundant isoform, is activated by DNA breaks and catalyzes the post-translational modification of proteins. It forms polymers ofADP-ribose and attaches them to acceptor proteins, including histones, DNA repair proteins, transcription factors. PARP-1 is a key enzyme involved in a maintenance of genomic stability. Excessive activation of the enzyme has been shown to contribute to tissue injury and inflammatory disorders. PARP is a key mediator of cell death in oxidative stress, ischemia and DNA damage. It also promotes the activation ofproinflammatory gene expression. Inhibition of PARP-1 provides significant protection in animal models of cardiovascular, autoimmune and inflammatory diseases. PARP inhibitors have shown antitumor activity because they compromise ability of cancer cells to repair DNA. PARP-1 is a promising therapeutic target.