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Neurogenesis in response to synthetic retinoids at different temporal scales.

Haffez, H. and Khatib, T. and McCaffery, P. and Przyborski, S. and Redfern, C. and Whiting, A. (2018) 'Neurogenesis in response to synthetic retinoids at different temporal scales.', Molecular neurobiology., 55 (3). pp. 1942-1950.

Abstract

All-trans retinoic acid (ATRA) plays key roles in neurogenesis mediated by retinoic acid receptors (RARs). RARs are important targets for the therapeutic regulation of neurogenesis but effective drug development depends on modelling-based strategies to design high-specificity ligands in combination with good biological assays to discriminate between target-specificity and off-target effects. Using neuronal differentiation as a model, the aim of this study was to test the hypothesis that responses across different temporal scales and assay platforms can be used as comparable measures of retinoid activity. In biological assays based on cell phenotype or behaviour, two structurally similar synthetic retinoids, differing in RAR affinity and specificity, retained their relative activities across different temporal scales. In contrast, assays based on the transcriptional activation of specific genes in their normal genomic context were less concordant with biological assays. Gene-induction assays for retinoid activity as modulators of neurogenesis require careful interpretation in the light of variation in ligand-receptor affinity, receptor expression and gene function. A better characterization of neuronal phenotypes and their regulation by retinoids is badly needed as a framework for understanding how to regulate neuronal development.

Item Type:Article
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Status:Peer-reviewed
Publisher Web site:https://doi.org/10.1007/s12035-017-0440-7
Publisher statement:© The Author(s) 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
Date accepted:03 February 2017
Date deposited:28 February 2017
Date of first online publication:27 February 2017
Date first made open access:No date available

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