Poly(ADP-ribose) Polymerase Inhibition in Acute Lung Injury: A Re-emerging Concept.

Poly(ADP-ribose) Polymerase Inhibition in Acute Lung Injury: A Re-emerging Concept. Am J Respir Cell Mol Biol. 2020 Jul 08;: Authors: Szabo C, Martins V, Liaudet L Abstract Poly(ADP-ribose) polymerase 1 (PARP1), the major isoform of a family of ADP-ribosylating enzymes, has been implicated in the regulation of various biological processes including DNA repair, gene transcription and cell death. The concept that PARP1 becomes activated in acute lung injury (ALI), and pharmacological inhibition or genetic deletion of this enzyme can provide therapeutic benefits has emerged over 20 years ago. The current article provides an overview of the cellular mechanisms involved in the pathogenetic roles of PARP1 in ALI, and overviews the preclinical data supporting the efficacy of PARP inhibitors. In recent years, several ultrapotent PARP inhibitors have been approved for clinical use (for the therapy of various oncological diseases): these newly-approved PARP inhibitors were recently reported to show efficacy in animal models of ALI. These observations offer the possibility of therapeutic repurposing of these inhibitors for patients with ALI. The current article lays out a potential roadmap for such repurposing efforts. In addition, the article also overviews the scientific basis of potentially applying PARP inhibitors for the experimental therapy of viral ALI, such as COVID-19-associated ARDS. PMID: 32640172 [PubMed - as supplied by pub...
Source: Am J Respir Cell Mol... - Category: Respiratory Medicine Authors: Tags: Am J Respir Cell Mol Biol Source Type: research