The role of HDAC3 in inflammation: mechanisms and therapeutic implications
Noah Watson1, Sivaraman Kuppuswamy1, William Luke Ledford1
1Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta University, Augusta, GA, United States.
Insights
Histone deacetylases (HDACs) regulate inflammation. This review focuses on HDAC3, highlighting its role in various inflammatory diseases and the potential benefits of its selective inhibition.
Area of Science:
- Molecular Biology
- Immunology
- Pharmacology
Background:
- Histone deacetylases (HDACs) are key regulators of inflammatory gene expression.
- Pan-HDAC inhibitors show efficacy in diseases, but their precise role in inflammation is unclear.
- Isoform-specific targeting of HDACs may reduce off-target effects.
Purpose of the Study:
- To review the role of HDAC3 in modulating inflammatory responses.
- To discuss the molecular mechanisms of HDAC3 in inflammation-associated pathologies.
- To identify knowledge gaps for future research.
Main Methods:
- Literature review of studies on HDAC3 and inflammation.
- Analysis of molecular mechanisms underlying HDAC3's inflammatory regulation.
- Synthesis of findings across various disease contexts.
Main Results:
- HDAC3 plays a significant role in modulating inflammatory responses.
- HDAC3 is implicated in brain pathology, arthritis, cardiovascular diseases, lung pathology, allergic conditions, and kidney disorders.
- Selective inhibition of HDAC3 shows beneficial effects in various inflammatory pathologies.
Conclusions:
- HDAC3 is a critical regulator of inflammation with diverse roles in disease.
- Targeting HDAC3 selectively offers a promising therapeutic strategy for inflammatory conditions.
- Further investigation is needed to explore HDAC3 inhibition for improved disease prognosis.
Abstract:
Histone deacetylases (HDACs) are critical regulators of inflammatory gene expression, and the efficacy of pan-HDAC inhibitors has been implicated in various disease conditions. However, it remains largely unclear how HDACs precisely regulate inflammation. To this end, evaluating the isoform-specific function of HDACs is critical, and the isoform-specific targeting could also circumvent the off-target effects of pan-HDAC inhibitors. This review provides an overview of the roles of HDAC3, a class I HDAC isoform, in modulating inflammatory responses and discusses the molecular mechanisms by which HDAC3 regulates inflammation associated with brain pathology, arthritis, cardiovascular diseases, lung pathology, allergic conditions, and kidney disorders. The articles also identify knowledge gaps in the field for future studies. Despite some conflicting reports, the selective inhibition of HDAC3 has been demonstrated to play a beneficial role in various inflammatory pathologies. Exploring the potential of HDAC3 inhibition to improve disease prognosis is a promising avenue requiring further investigation.
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