Jin Ping, Duan Xirui, Huang Zhao, Dong Yuan, Zhu Jianmei, Guo Huiming, Tian Hui, Zou Cheng-Gang, Xie Ke
State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan and Key Laboratory of Industrial Microbial Fermentation Engineering of Yunnan Province, School of Life Sciences, Yunnan University, Kunming, China.
Department of Oncology, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine; Shanghai Key Laboratory of Gastric Neoplasms, Shanghai, China.
Signal Transduct Target Ther. 2025 Jul 28;10(1):228. doi: 10.1038/s41392-025-02270-3.
Nuclear receptors (NRs) are a large family of ligand-dependent transcription factors that regulate the expression of a wide range of target genes in response to endogenous and exogenous ligands, including steroid hormones, thyroid hormone, vitamin D, retinoic acid, fatty acids, and oxidative steroids. Upon ligand binding, nuclear receptors form dimer complexes with transcriptional cofactors, which interact with specific DNA sequences in the promoter or enhancer regions of target genes to modulate gene expression. This process plays a crucial role in many physiological processes such as reproduction, development, immune responses, metabolism, and homeostasis. Dysregulation of nuclear receptor signaling is implicated in the pathogenesis of numerous diseases, including cancers, metabolic disorders, cardiovascular diseases, and autoimmune conditions. Therefore, understanding the molecular mechanisms underlying nuclear receptor functions is essential for the development of novel therapeutic strategies. This review summarizes the current understanding of nuclear receptors in both physiological and pathological contexts, providing insights into the signaling pathways they regulate. Additionally, we discuss recent advances in drug development targeting nuclear receptors, with a focus on preclinical and clinical studies aimed at improving therapeutic efficacy. By exploring these therapeutic avenues, this article highlights the potential of nuclear receptors as promising targets for future treatments of a variety of human diseases, paving the way for more personalized and effective therapies in clinical medicine.
核受体（NRs）是一类庞大的依赖配体的转录因子家族，它们可响应内源性和外源性配体（包括类固醇激素、甲状腺激素、维生素D、视黄酸、脂肪酸和氧化类固醇）来调节多种靶基因的表达。配体结合后，核受体与转录辅因子形成二聚体复合物，这些转录辅因子与靶基因启动子或增强子区域的特定DNA序列相互作用，从而调节基因表达。这一过程在许多生理过程中发挥着关键作用，如生殖、发育、免疫反应、代谢和体内平衡。核受体信号传导失调与多种疾病的发病机制有关，包括癌症、代谢紊乱、心血管疾病和自身免疫性疾病。因此，了解核受体功能的分子机制对于开发新的治疗策略至关重要。本综述总结了目前在生理和病理背景下对核受体的认识，深入探讨了它们所调节的信号通路。此外，我们讨论了针对核受体的药物开发的最新进展，重点关注旨在提高治疗效果的临床前和临床研究。通过探索这些治疗途径，本文强调了核受体作为未来治疗多种人类疾病的有前景靶点的潜力，为临床医学中更个性化和有效的治疗铺平道路。
