Mandeep Kaur and Saurabh Sharma
Recent studies have clearly indicated that Poly (ADP-Ribose) Polymerase (PARP) has an essential role in various physiological and pathophysiological pathways including the signaling of DNA damage, cell death pathways, cell survival and proliferation pathways, differentiation, neuronal function and inflammation. Role of PARP has been established in cardiovascular diseases like myocardial infarction, endothelial dysfunction associated hypertension, ischemia-reperfusion injury. It also plays an important role in the pathophysiology of diabetes, inflammatory disorders, and various neurodegenerative disorders. Approaches in this area lead to the identification of 18 putative PARP sequences in the human genome. PARP-1 is a most abundantly found nuclear protein which functions to sense the DNA damage. Increased oxidative stress due to any pathophysiological condition in the body, leads to over-activation of PARP1. Over-activation of PARP1 decreases the amount of NAD+/ATP in the cell and also leads to translocation of Apoptosis-Inducing Factor (AIF) to the nucleus causing cell dysfunction and ultimately cell death. Pharmacological inhibition of PARP provides a target for the prevention of various pathological conditions because it targets a relatively late event of oxidative cell injury. Therefore, investigations on the involvement of PARP and its isoforms in diseased conditions substantiate the therapeutic window of intervention quite wide.