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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.
Abstract:
Aberrant adenosine diphosphate-ribose (ADP)-ribosylation of proteins and nucleic acids is associated with multiple disease processes such as infections and chronic inflammatory diseases. The poly(ADP-ribose) polymerase (PARP)/ADP-ribosyltransferase (ART) family members promote mono- or poly-ADP-ribosylation. Although evidence has linked PARPs/ARTs and macrophages in the context of chronic inflammation, the underlying mechanisms remain incompletely understood. This review provides an overview of literature focusing on the roles of PARP1/ARTD1, PARP7/ARTD14, PARP9/ARTD9, and PARP14/ARTD8 in macrophages. PARPs/ARTs regulate changes in macrophages during chronic inflammatory processes not only via catalytic modifications but also via non-catalytic mechanisms. Untangling complex mechanisms, by which PARPs/ARTs modulate macrophage phenotype, and providing molecular bases for the development of new therapeutics require the development and implementation of innovative technologies.
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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