Poly(adenosine diphosphate-ribose) polymerase as therapeutic target: lessons learned from its inhibitors.
Poly(ADP-ribose) polymerases are a family of DNA-dependent nuclear enzymes catalyzing the transfer of ADP-ribose moieties from cellular nicotinamide-adenine-dinucleotide to a variety of target proteins. Although they have been considered as resident nuclear elements of the DNA repair machinery, recent works revealed a more intricate physiologic role of poly(ADP-ribose) polymerases with numerous extranuclear activities. Indeed, poly(ADP-ribose) polymerases participate in fundamental cellular processes like chromatin remodelling, transcription or regulation of the cell-cycle. These new insight into the physiologic roles of poly(ADP-ribose) polymerases widens the range of human pathologies in which pharmacologic inhibition of these enzymes might have a therapeutic potential. Here, we overview our current knowledge on extranuclear functions of poly(ADP-ribose) polymerases with a particular focus on the mitochondrial ones and discuss potential fields of future clinical applications.
['Cseh|Anna Mária|AM|', 'Fábián|Zsolt|Z|', 'Sümegi|Balázs|B|', 'Scorrano|Luca|L|']
D006801:Humans D008928:Mitochondria D011065:Poly(ADP-ribose) Polymerases D015398:Signal Transduction
PARP cancer mitochondria signaling targeted therapy