Hartman Institute for Therapeutic Organ Regeneration

Retinoic acid signaling pathways in development and diseases.

TitleRetinoic acid signaling pathways in development and diseases.
Publication TypeJournal Article
Year of Publication2014
AuthorsDas BC, Thapa P, Karki R, Das S, Mahapatra S, Liu T-C, Torregroza I, Wallace DP, Kambhampati S, Van Veldhuizen P, Verma A, Ray SK, Evans T
JournalBioorg Med Chem
Volume22
Issue2
Pagination673-83
Date Published2014 Jan 15
ISSN1464-3391
KeywordsAging, Animals, Drug Discovery, Eye, Humans, Kidney, Metabolic Diseases, Molecular Structure, Neoplasms, Signal Transduction, Tretinoin
Abstract

<p>Retinoids comprise a group of compounds each composed of three basic parts: a trimethylated cyclohexene ring that is a bulky hydrophobic group, a conjugated tetraene side chain that functions as a linker unit, and a polar carbon-oxygen functional group. Biochemical conversion of carotenoid or other retinoids to retinoic acid (RA) is essential for normal regulation of a wide range of biological processes including development, differentiation, proliferation, and apoptosis. Retinoids regulate various physiological outputs by binding to nuclear receptors called retinoic acid receptors (RARs) and retinoid X receptors (RXRs), which themselves are DNA-binding transcriptional regulators. The functional response of RA and their receptors are modulated by a host of coactivators and corepressors. Retinoids are essential in the development and function of several organ systems; however, deregulated retinoid signaling can contribute to serious diseases. Several natural and synthetic retinoids are in clinical use or undergoing trials for treating specific diseases including cancer. In this review, we provide a broad overview on the importance of retinoids in development and various diseases, highlighting various retinoids in the drug discovery process, ranging all the way from retinoid chemistry to clinical uses and imaging.</p>

DOI10.1016/j.bmc.2013.11.025
Alternate JournalBioorg Med Chem
PubMed ID24393720
PubMed Central IDPMC4447240
Grant ListHL56182 / HL / NHLBI NIH HHS / United States
AI093220 / AI / NIAID NIH HHS / United States
R56 AI093220 / AI / NIAID NIH HHS / United States
R01 HL111400 / HL / NHLBI NIH HHS / United States
AA020630 / AA / NIAAA NIH HHS / United States
R01 DK081579 / DK / NIDDK NIH HHS / United States
HL111400 / HL / NHLBI NIH HHS / United States
R37 HL056182 / HL / NHLBI NIH HHS / United States
R21 AA020630 / AA / NIAAA NIH HHS / United States
R01 HL056182 / HL / NHLBI NIH HHS / United States
DK081579 / DK / NIDDK NIH HHS / United States

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