Targeting histone deacetylases for the treatment of disease.
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.
Lawless
M W
MW
Centre for Liver Disease, School of Medicine and Medical Science, Mater Misericordiae University Hospital - University College Dublin, Dublin, Ireland.
Norris
S
S
O'Byrne
K J
KJ
Gray
S G
SG
D000107:Acetylation; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000201:enzymology*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D051548:Histone Acetyltransferases / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology*; D011499:Protein Processing, Post-Translational
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D056572:Histone Deacetylase Inhibitors; D007004:Hypoglycemic Agents; D051548:Histone Acetyltransferases; D006655:Histone Deacetylases