Dorien Clarisse , Laura Van Moortel , Chloé Van Leene , Kris Gevaert , Karolien De Bosscher
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引用次数: 0
Abstract
The glucocorticoid receptor (GR) is a major nuclear receptor (NR) drug target for the treatment of inflammatory disorders and several cancers. Despite the effectiveness of GR ligands, their systemic action triggers a plethora of side effects, limiting long-term use. Here, we discuss new concepts of and insights into GR mechanisms of action to assist in the identification of routes toward enhanced therapeutic benefits. We zoom in on the communication between different GR domains and how this is influenced by different ligands. We detail findings on the interaction between GR and chromatin, and highlight how condensate formation and coregulator confinement can perturb GR transcriptional responses. Last, we discuss the potential of novel ligands and the therapeutic exploitation of crosstalk with other NRs.
糖皮质激素受体（GR）是治疗炎症性疾病和多种癌症的主要核受体（NR）药物靶点。尽管 GR 配体很有效，但其全身作用会引发大量副作用，限制了长期使用。在此，我们将讨论有关 GR 作用机制的新概念和新见解，以帮助确定提高治疗效果的途径。我们将深入探讨不同 GR 结构域之间的交流，以及不同配体如何影响这种交流。我们详细介绍了 GR 与染色质之间相互作用的发现，并强调了凝集物的形成和核心调节剂的限制如何扰乱 GR 的转录反应。最后，我们讨论了新型配体的潜力以及利用与其他 NRs 的串扰进行治疗的可能性。
期刊介绍：
For over 40 years, Trends in Biochemical Sciences (TIBS) has been a leading publication keeping readers informed about recent advances in all areas of biochemistry and molecular biology. Through monthly, peer-reviewed issues, TIBS covers a wide range of topics, from traditional subjects like protein structure and function to emerging areas in signaling and metabolism. Articles are curated by the Editor and authored by top researchers in their fields, with a focus on moving beyond simple literature summaries to providing novel insights and perspectives. Each issue primarily features concise and timely Reviews and Opinions, supplemented by shorter articles including Spotlights, Forums, and Technology of the Month, as well as impactful pieces like Science & Society and Scientific Life articles.
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