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Bile Acids as Novel Pharmacological Agents: the Interplay between Gene Polymorphisms, Epigenetic Factors and Drug Response
- Source :
- Current Pharmaceutical Design. 22:1-1
- Publication Year :
- 2016
- Publisher :
- Bentham Science Publishers Ltd., 2016.
-
Abstract
- Background: The field of bile acid research has become tremendously active. Bile acids have been shown to act as signaling molecules that are involved in many metabolic processes, but their role in carcinogenesis is also emerging. Methods: The aim of this review was to summarize the present knowledge in the innovative field of bile acids pharmacology, to reveal the novel mechanisms of their action, particularly focusing on clinically relevant aspects, and to evaluate the role of both genetic and epigenetic variation in genes encoding bile acid-activated receptors in determining the therapy outcome. Results: Most effects of bile acids are mediated by both nuclear and G protein-coupled receptors. Three natural bile acids have already been registered for the use in humans, but various semi-synthetic bile acid analogues with improved pharmacokinetic and pharmacodynamic properties have been developed, which opens up new avenues in pharmacotherapy. Many efforts have been made to evaluate the impact of nuclear receptors on inter-individual variation in responses to drugs, since nuclear receptors are significant mediators between environmental stimuli and pharmacokinetics. Genetic variation of bile acid-activated receptors is associated with both benign and malignant diseases, in terms of disease risk and severity, but also with pharmacokinetics and therapy outcome. Furthermore, the activity of these receptors may be masked or amplified by epigenetic modifications. Conclusion: Both genetic and epigenetic factors may alter complex and intricate network of bile acid signaling pathways, contributing to the development of several metabolic and non-metabolic diseases and altered activities of drug-metabolizing enzymes and transporters. These polymorphisms and epigenetic modifications may also impact the effectiveness and pharmacokinetics of bile acid analogues, which must be taken into account during the development of these compounds as novel therapeutic agents.
- Subjects :
- 0301 basic medicine
030103 biophysics
Cell signaling
medicine.drug_class
Receptors, Cytoplasmic and Nuclear
010501 environmental sciences
Biology
Pharmacology
01 natural sciences
Epigenesis, Genetic
Bile Acids and Salts
03 medical and health sciences
Neoplasms
Drug Discovery
medicine
Animals
Humans
Obesity
Epigenetics
Receptor
0105 earth and related environmental sciences
Polymorphism, Genetic
Bile acid
Liver Diseases
Atherosclerosis
G protein-coupled bile acid receptor
Diabetes Mellitus, Type 2
Drug development
Farnesoid X receptor
Signal transduction
Subjects
Details
- ISSN :
- 13816128
- Volume :
- 22
- Database :
- OpenAIRE
- Journal :
- Current Pharmaceutical Design
- Accession number :
- edsair.doi.dedup.....4e55e6ab11d903ab0c4b2b700e9d96d6