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Nat Rev Gastroenterol Hepatol. 2014 Jan;11(1):55-67. doi: 10.1038/nrgastro.2013.151. Epub 2013 Aug 27.

Bile acid receptors as targets for drug development.

Author information

1
Department of Surgery, NUTRIM School of Nutrition, Toxicology and Metabolism, Maastricht University, PO Box 616, 6200 MD, Maastricht, Netherlands.
2
Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.
3
Department of Gastroenterology and Hepatology, Academic Medical Centre, Meibergdreef 9, 1105 AZ, Amsterdam, Netherlands.

Abstract

The intracellular nuclear receptor farnesoid X receptor and the transmembrane G protein-coupled receptor TGR5 respond to bile acids by activating transcriptional networks and/or signalling cascades. These cascades affect the expression of a great number of target genes relevant for bile acid, cholesterol, lipid and carbohydrate metabolism, as well as genes involved in inflammation, fibrosis and carcinogenesis. Pregnane X receptor, vitamin D receptor and constitutive androstane receptor are additional nuclear receptors that respond to bile acids, albeit to a more restricted set of species of bile acids. Recognition of dedicated bile acid receptors prompted the development of semi-synthetic bile acid analogues and nonsteroidal compounds that target these receptors. These agents hold promise to become a new class of drugs for the treatment of chronic liver disease, hepatocellular cancer and extrahepatic inflammatory and metabolic diseases. This Review discusses the relevant bile acid receptors, the new drugs that target bile acid signalling and their possible applications.

PMID:
23982684
DOI:
10.1038/nrgastro.2013.151
[Indexed for MEDLINE]
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