IMR Press / FBS / Volume 8 / Issue 1 / DOI: 10.2741/S452

Frontiers in Bioscience-Scholar (FBS) is published by IMR Press from Volume 13 Issue 1 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on as a courtesy and upon agreement with Frontiers in Bioscience.


Alternative mechanisms of inhibiting activity of poly (ADP-ribose) polymerase-1

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1 Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Narkachal Hilltop, Bhangagarh, Guwahati, Assam, India, PIN 78103
2 Department of Pharmacology, Gauhati Medical College, Narkachal Hilltop, Bhangagarh, Guwahati, Assam, India
3 IMS Health, Mumbai, Maharashtra, India

*Author to whom correspondence should be addressed.

Front. Biosci. (Schol Ed) 2016, 8(1), 123–128;
Published: 1 January 2016

Poly ADP-ribose polymerase (PARP-1), a DNA nick-sensor enzyme, is an abundant nuclear protein. Upon sensing DNA breaks, PARP-1 gets activated and cleaves NAD into nicotinamide and ADP-ribose and polymerizes the latter onto nuclear acceptor proteins including histones, transcription factors, and PARP-1 itself. Poly(ADP-ribosylation) mainly contributes to DNA repairing mechanism. However, oxidative stress-induced over-activation of PARP-1 consumes excess of NAD and consequently ATP, culminating into cell necrosis. This cellular suicide pathway has been implicated in several conditions such as stroke, myocardial ischemia, diabetes. Thus, it can be a rationale approach to inhibit the activity of PARP-1 for reducing detrimental effects associated with oxidative stress-induced over-activation of PARP-1. Several preclinical as well as clinical studies of PARP-1 inhibitors have been used in conditions such as cancer, stroke and traumatic brain injury. Conventionally, there are many studies which employed the concept of direct inhibition of PARP-1 by competing with NAD. Here, in the present review, we highlight several prospective alternative approaches for the inhibition of PARP-1 activity.

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