Targeting histone deacetylases for the treatment of disease

Introduction HATs/HDACs and the pro‐inflammatory environment HATs/HDACs and endoplasmic reticulum (ER) stress The potential role of histone deacetylase inhibitors in the treatment of cancer Potential role of histone deacetylase inhibitors in the treatment of diabetes The potential role of histone deacetylase inhibitors in the treatment of neurodegenerative conditions Histone deacetylase inhibitors Caveats Final comments Abstract The ‘histone code’ is a well‐established hypothesis describing the idea that specific patterns of post‐translational modifications to histones act like a molecular ‘code’ recognized and used by non‐histone proteins to regulate specific chromatin functions. One modification, which has received significant attention, is that of histone acetylation. The enzymes that regulate this modification are described as lysine acetyltransferases or KATs, and histone deacetylases or HDACs. Due to their conserved catalytic domain HDACs have been actively targeted as a therapeutic target. The pro‐inflammatory environment is increasingly being recognized as a critical element for both degenerative diseases and cancer. The present review will discuss the current knowledge surrounding the clinical potential and current development of histone deacetylases for the treatment of diseases for which a pro‐inflammatory environment plays important roles, and the molecular mechanisms by which such inhibitors may play important functions in modulating the pro‐inflammatory environment.