Poly (ADP-ribose) polymerase: An Overview of Mechanistic Approaches and Therapeutic Opportunities in the Management of Stroke

Abstract

Stroke is one of the leading causes of morbidity and mortality accompanied by blood supply loss to a particular brain area. Several mechanistic approaches such as inhibition of poly (ADP-ribose) polymerase, therapies against tissuethrombosis, and neutrophils lead to stroke's therapeutic intervention. Evidenceobtained with the poly (ADP-ribose) polymerase (PARP) inhibition and animalshaving a deficiency of PARP enzymes; represented the role of PARP in cerebral stroke, ischemia/reperfusion, and neurotrauma. PARP is a nuclear enzyme superfamily with various isoforms, each with different structural domains and functions, and out of all, PARP-1 is thebest-characterized member. It has been shown to perform multiple physiological as well as pathological processes, including its role in inflammation, oxidative stress, apoptosis, and mitochondrial dysfunction. The enzyme interacts with NF-κB, p53, and other transcriptional factors to regulate survival and cell death and modulates multiple downstream signaling pathways. Clinical trials have also been conducted using PARP inhibitors for numerous disorders and have shown positive results. However, additional information is yet to be established for the therapeutic intervention of PARP inhibitors in stroke. These agents' utilization appears to be challenging due to their unknown potential long-term side effects. PARP activity increased during ischemia, but its inhibition provided significant neuroprotection. Despite the increased interest in PARP as a pharmacological modulator for novel therapeutic therapies, the current review focused on stroke and poly ADP-ribosylation.