Targeting histone deacetylases for the treatment of immune, endocrine & metabolic disorders.
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" recognised 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 which regulate this modification are described as histone acetyltransferases or HATs, and histone deacetylases or HDACs [1]. Due to their conserved catalytic domain HDACs have been actively targeted as a therapeutic target. The pro-inflammatory environment is increasingly being recognised as a critical element for both degenerative diseases and cancer. The present review will discuss the current knowledge surrounding the clinical potential & current development of histone deacetylases for the treatment of diseases for which a proinflammatory environment plays important roles, and the molecular mechanisms by which such inhibitors may play important functions in modulating the proinflammatory environment.
Lawless
M W
MW
Department of Clinical Medicine, Trinity Centre for Health Sciences, Dublin, Ireland.
Norris
S
S
O'Byrne
K J
KJ
Gray
S G
SG
D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy*; D003920:Diabetes Mellitus / Q000188:drug therapy*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy*; D009103:Multiple Sclerosis / Q000188:drug therapy*; D016328:NF-kappa B / Q000502:physiology; D010190:Pancreatic Neoplasms / Q000188:drug therapy*
D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D016328:NF-kappa B