Poly (ADP-ribose) polymerase-1 as a promising drug target for neurodegenerative diseases

Poly (ADP-ribose) polymerase- (PARP)-1 is predominantly triggered by DNA damage. Overexpression of PARP-1 is known for its association with the pathogenesis of several CNS disorders, such as Stroke, Parkinson's disease (PD), Alzheimer's disease (AD), Huntington (HD) and Amyotrophic lateral sclerosis (ALS). NAD+ depletion resulted PARP related cell death only happened when the trial used extreme high oxidization treatment. Inhibition of PARP1/2 may induce replication related cell death due to un-repaired DNA damage. This review has discussed PARP-1 modulated downstream pathways in neurodegeneration and various FDA approved PARP-1 inhibitors. A systematic literature review of PubMed, Medline, Bentham, Scopus and EMBASE (Elsevier) databases was carried out to understand the nature of the extensive work done on mechanistic role of Poly (ADP-ribose) polymerase and its inhibition in Neurodegenerative diseases. Several researchers have put forward number of potential treatments, of which PARP-1 enzyme has been regarded as a potent target intended for the handling of neurodegenerative ailments. Targeting PARP using its chemical inhibitors in various neurodegenerative may have therapeutic outcomes by reducing neuronal death mediated by PARPi. Numerous PARP-1 inhibitors have been studied in neurodegenerative diseases but they haven't been clinically evaluated. In this review, the pathological role of PARP-1 in various neurodegenerative diseases has been discussed along with the therapeutic role of PARP-1 inhibitors in various neurodegenerative diseases. [Display omitted] •Parthanatos involves cell death mechanism which is dependent on PARP activation in response to any stress and toxic stimuli.•Parthanatos and its cellular responses such as apoptosis, cell survival, and differentiation are involved in this study.•Involvement of PARP-1 in various neurodegenerative diseases such as such as Parkinson's, Alzheimer, Huntington and ALS.•Downstream pathways (Caspase, PI3K, NF-κB and ASK-1 signalling) are modulated by PARP-1 in neurodegeneration.•Various PARP-1 inhibitors in neuroprotection proved to be a potential target in NDD.