Histone deacetylases as targets for treatment of multiple diseases

Abstract

HDACs (histone deacetylases) are a group of enzymes that deacetylate histones as well as non-histone proteins. They are known as modulators of gene transcription and are associated with proliferation and differentiation of a variety of cell types and the pathogenesis of some diseases. Recently, HDACs have come to be considered crucial targets in various diseases, including cancer, interstitial fibrosis, autoimmune and inflammatory diseases, and metabolic disorders. Pharmacological inhibitors of HDACs have been used or tested to treat those diseases. In the present review, we will examine the application of HDAC inhibitors in a variety of diseases with the focus on their effects of anti-cancer, fibrosis, anti-inflammatory, immunomodulatory activity and regulating metabolic disorders.

Figure 1. HDACI targets and downstream effects

Inhibition of HDACs by HDACIs induces acetylation of histone proteins, as well as non-histone proteins, which leads to the alteration in various physiological and pathological processes, including apoptosis/autophagy, cell cycle, fibrogenesis, immune response, inflammation and metabolism. Therefore HDACIs may be potent therapeutic agents for anticancer, antifibrosis, anti-inflammatory and immunomodulation, and regulating metabolic disorders.