The Role of PARPs in Inflammation-and Metabolic-Related Diseases: Molecular Mechanisms and Beyond

Cells. 2019 Sep 6;8(9):1047. doi: 10.3390/cells8091047.

Abstract

Poly(ADP-ribosyl)ation (PARylation) is an essential post-translational modification catalyzed by poly(ADP-ribose) polymerase (PARP) enzymes. Poly(ADP-ribose) polymerase 1 (PARP1) is a well-characterized member of the PARP family. PARP1 plays a crucial role in multiple biological processes and PARP1 activation contributes to the development of various inflammatory and malignant disorders, including lung inflammatory disorders, cardiovascular disease, ovarian cancer, breast cancer, and diabetes. In this review, we will focus on the role and molecular mechanisms of PARPs enzymes in inflammation- and metabolic-related diseases. Specifically, we discuss the molecular mechanisms and signaling pathways that PARP1 is associated with in the regulation of pathogenesis. Recently, increasing evidence suggests that PARP inhibition is a promising strategy for intervention of some diseases. Thus, our in-depth understanding of the mechanism of how PARPs are activated and how their signaling downstream effecters can provide more potential therapeutic targets for the treatment of the related diseases in the future is crucial.

Keywords: PARP1; cancer; inflammation; metabolism; poly(ADP)-ribosylation; therapeutic approaches.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Humans
  • Inflammation / metabolism
  • Inflammation / physiopathology
  • Metabolic Diseases / metabolism
  • Metabolic Diseases / physiopathology
  • Poly ADP Ribosylation / physiology*
  • Poly Adenosine Diphosphate Ribose / metabolism
  • Poly(ADP-ribose) Polymerase Inhibitors
  • Poly(ADP-ribose) Polymerases / genetics
  • Poly(ADP-ribose) Polymerases / metabolism*
  • Poly(ADP-ribose) Polymerases / physiology*
  • Protein Processing, Post-Translational
  • Signal Transduction

Substances

  • Poly(ADP-ribose) Polymerase Inhibitors
  • Poly Adenosine Diphosphate Ribose
  • Poly(ADP-ribose) Polymerases