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Glucocorticoid hedgehog agonists in neurogenesis.

机译:糖皮质激素刺猬蛋白激动剂在神经发生中的作用。

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摘要

The process of neurogenesis in mammals, which is prolific and widespread at birth, gradually slows with aging and in humans becomes restricted to areas including the cerebellum and hippocampus. It has been reported that exposure to glucocorticoids can impair neurogenesis in both adults and children. Glucocorticoids are known to bind with high affinity to intracellular receptors. Glucocorticoid blood levels are normally regulated by environmental stresses, but because of their clinical utility, exogenous glucocorticoids are frequently administered in drug formulations. Consequently, concerns have arisen about the consequences of glucocorticoid use on neurogenesis and health, especially in the pediatric population. In this article, we will review recent findings that a select number of related glucocorticoids, halcinonide, fluticasone propionate, clobetasol propionate, and fluocinonide, also bind the hedgehog pathway receptor Smoothened. We will discuss their pharmacology and also a most surprising resu that this select group of compounds, which includes FDA approved drugs, unlike typical glucocorticoids such as dexamethasone, stimulate stem cell growth, and thus enhance neurogenesis.
机译:哺乳动物的神经发生过程多产且广泛分布,随着年龄的增长而逐渐减慢,而在人类中则局限于小脑和海马等区域。据报道,糖皮质激素的暴露可损害成人和儿童的神经发生。已知糖皮质激素与细胞内受体具有高亲和力结合。糖皮质激素的血液水平通常受环境压力的调节,但是由于其临床实用性,外源糖皮质激素经常以药物制剂的形式给药。因此,人们开始担心使用糖皮质激素对神经发生和健康的影响,尤其是在儿科人群中。在本文中,我们将回顾最近的发现,即一些相关的糖皮质激素,烟碱类,丙酸氟替卡松,丙酸氯倍他索和氟考尼特也结合了刺猬通路受体“ Smoothed”。我们将讨论它们的药理作用以及最令人惊讶的结果。与典型的糖皮质激素(如地塞米松)不同,该选择的化合物组(包括FDA批准的药物)刺激干细胞生长,从而增强神经发生。

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