PARPs and ADP-Ribosylation in Chronic Inflammation: A Focus on Macrophages

Diego V Santinelli-Pestana1, Elena Aikawa1,2, Sasha A Singh1

  • 1Center for Interdisciplinary Cardiovascular Sciences, Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.

PubMed

Insights

Aberrant ADP-ribosylation by poly(ADP-ribose) polymerase (PARP)/ADP-ribosyltransferase (ART) enzymes impacts chronic inflammation. This review explores PARP/ART roles in macrophages, highlighting catalytic and non-catalytic mechanisms for therapeutic development.

Area of Science:

  • Biochemistry
  • Immunology
  • Molecular Biology

Background:

  • Aberrant ADP-ribosylation is implicated in diseases like infections and chronic inflammation.
  • Poly(ADP-ribose) polymerase (PARP)/ADP-ribosyltransferase (ART) enzymes catalyze ADP-ribosylation.
  • The specific roles of PARPs/ARTs in macrophage function during chronic inflammation require further elucidation.

Purpose of the Study:

  • To review the literature on the roles of specific PARP/ART family members in macrophages.
  • To explore both catalytic and non-catalytic mechanisms by which PARPs/ARTs influence macrophage phenotype.
  • To identify knowledge gaps and suggest future research directions for therapeutic development.

Main Methods:

  • Literature review focusing on PARP1/ARTD1, PARP7/ARTD14, PARP9/ARTD9, and PARP14/ARTD8.
  • Analysis of existing studies on PARP/ART function in macrophage biology.
  • Synthesis of information regarding catalytic and non-catalytic roles.

Main Results:

  • PARPs/ARTs significantly modulate macrophage phenotypes during chronic inflammatory processes.
  • Both enzymatic activity and non-catalytic functions of PARPs/ARTs are crucial in regulating macrophages.
  • Specific PARP/ART members like PARP1/ARTD1, PARP7/ARTD14, PARP9/ARTD9, and PARP14/ARTD8 are key players.

Conclusions:

  • PARPs/ARTs are critical regulators of macrophage responses in chronic inflammation.
  • Understanding the complex catalytic and non-catalytic mechanisms is essential for therapeutic targeting.
  • Innovative technologies are needed to fully unravel these intricate molecular pathways.

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