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Histone deacetylases and their inhibitors in cancer, neurological diseases and immune disorders
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Journal Article
Histone deacetylases and their inhibitors in cancer, neurological diseases and immune disorders
2014
Overview
Key Points
Epigenetic deregulation can underpin the onset and progression of several human diseases.
The expression and/or function of histone deacetylases (HDACs) is often perturbed in cancer, neurological syndromes and immune disorders.
HDACs can be effectively targeted using small-molecule chemical compounds, and more selective agents are currently being developed and further tested.
Histones are not the only substrates of HDACs, and altered acetylation of diverse cellular proteins may be important in disease aetiology and the response to HDAC inhibitors.
HDACs function as the catalytic subunits of large multiprotein complexes, and the molecular and biological consequences of HDAC inhibition need to be assessed in this context.
HDAC inhibitors have been approved for the treatment of certain haematological malignancies and are being clinically evaluated alone and in combination with other agents for efficacy in other cancer settings, in neurological diseases and in immune disorders such as autoimmunity.
Histone deacetylases (HDACs) are a class of epigenetic enzymes that remove acetyl groups from lysine residues on histones and other proteins. In this Review, the authors highlight the role of HDACs in cancer, neurological diseases and immune disorders, and discuss the development of small-molecule inhibitors.
Epigenetic aberrations, which are recognized as key drivers of several human diseases, are often caused by genetic defects that result in functional deregulation of epigenetic proteins, their altered expression and/or their atypical recruitment to certain gene promoters. Importantly, epigenetic changes are reversible, and epigenetic enzymes and regulatory proteins can be targeted using small molecules. This Review discusses the role of altered expression and/or function of one class of epigenetic regulators — histone deacetylases (HDACs) — and their role in cancer, neurological diseases and immune disorders. We highlight the development of small-molecule HDAC inhibitors and their use in the laboratory, in preclinical models and in the clinic.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 631/67
/ 692/308
/ 692/699
/ Analysis
/ Animals
/ Epigenesis, Genetic - drug effects
/ Epigenesis, Genetic - immunology
/ Histone Deacetylase Inhibitors - metabolism
/ Histone Deacetylase Inhibitors - pharmacology
/ Histone Deacetylase Inhibitors - therapeutic use
/ Histone Deacetylases - genetics
/ Histone Deacetylases - metabolism
/ Histone Deacetylases - physiology
/ Histones
/ Humans
/ Immune System Diseases - drug therapy
/ Immune System Diseases - immunology
/ Immune System Diseases - metabolism
/ Nervous System Diseases - drug therapy
/ Nervous System Diseases - immunology
