title: Alternative mechanisms of inhibiting activity of poly (ADP-ribose) polymerase-1.
abstract: 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.
authors.affiliation: Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Narkachal Hilltop, Bhangagarh, Guwahati, Assam, India. PIN: 781032, srshekhar@yahoo.com.
authors.forename: Chandra Shaker
authors.initials: CS
authors.lastname: Sriram
authors.affiliation: Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Narkachal Hilltop, Bhangagarh, Guwahati, Assam, India. PIN: 781032.
authors.forename: Ashok
authors.initials: A
authors.lastname: Jangra
authors.affiliation: Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Narkachal Hilltop, Bhangagarh, Guwahati, Assam, India. PIN: 781032.
authors.forename: Babul Kumar
authors.initials: BK
authors.lastname: Bezbaruah
authors.affiliation: Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Narkachal Hilltop, Bhangagarh, Guwahati, Assam, India. PIN: 781032.
authors.forename: Athira K
authors.initials: AK
authors.lastname: V
authors.affiliation: IMS Health, Mumbai, Maharashtra, India.
authors.forename: Shivaji
authors.initials: S
authors.lastname: Sykam
mesh_terms: D016923:Cell Death; D006801:Humans; D018384:Oxidative Stress; D000067856:Poly(ADP-ribose) Polymerase Inhibitors / Q000494:pharmacology*; D011065:Poly(ADP-ribose) Polymerases / Q000187:drug effects*
chemical_list: D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases