Neurogenesis in Response to Synthetic Retinoids at Different Temporal Scales.
Neurogenesis in Response to Synthetic Retinoids at Different Temporal Scales.
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DOI：
10.1007/s12035-017-0440-7
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发表时间：
2018-03
影响因子：
5.1
通讯作者：
Whiting A
中科院分区：
文献类型：
--
作者：
Haffez H;Khatib T;McCaffery P;Przyborski S;Redfern C;Whiting A
全反式维甲酸（ATRA）在维甲酸受体（RAR）介导的神经发生中起关键作用。RAR是神经发生治疗调节的重要靶点，但有效的药物开发取决于基于建模的策略，以设计高特异性配体，并结合良好的生物学测定来区分靶特异性和脱靶效应。使用神经元分化作为模型，本研究的目的是测试的假设，在不同的时间尺度和测定平台的反应可以用作类维生素A活性的可比措施。在基于细胞表型或行为的生物测定中，两种结构相似的合成类维生素A，在RAR亲和力和特异性方面不同，在不同的时间尺度上保留了它们的相对活性。相比之下，基于特定基因在其正常基因组背景下的转录激活的测定与生物测定不太一致。视黄酸作为神经发生调节剂的活性的基因诱导测定需要根据配体-受体亲和力、受体表达和基因功能的变化进行仔细解释。一个更好的表征神经元的表型和他们的调节类维生素A是迫切需要作为一个框架，了解如何调节神经元的发展。
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.
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影响因子：
--
作者：
Clemens, Graeme;Flower, Kevin R.;Przyborski, Stefan
通讯作者：
Przyborski, Stefan
影响因子：
--
作者：
Haffez, Hesham;Chisholm, David R.;Whiting, Andrew
通讯作者：
Whiting, Andrew
影响因子：
2.7
作者：
Okada, Y;Shimazaki, T;Okano, H
通讯作者：
Okano, H
影响因子：
4
作者：
Przyborski, SA;Christie, VB;Horrocks, GM
通讯作者：
Horrocks, GM
DOI：
10.1073/pnas.0511294103
发表时间：
2006-03-07
影响因子：
11.1
作者：
Jacobs, S;Lie, DC;Evans, RM
通讯作者：
Evans, RM