Nuclear receptors in health and disease: signaling pathways, biological functions and pharmaceutical interventions
Abstract 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 oxidativ...
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| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2025-07-01
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| Series: | Signal Transduction and Targeted Therapy |
| Online Access: | https://doi.org/10.1038/s41392-025-02270-3 |
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| author | Ping Jin Xirui Duan Zhao Huang Yuan Dong Jianmei Zhu Huiming Guo Hui Tian Cheng-Gang Zou Ke Xie |
| author_facet | Ping Jin Xirui Duan Zhao Huang Yuan Dong Jianmei Zhu Huiming Guo Hui Tian Cheng-Gang Zou Ke Xie |
| author_sort | Ping Jin |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-8bdd2f95e5ca4659a3190b900c43e67f |
| institution | Kabale University |
| issn | 2059-3635 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Signal Transduction and Targeted Therapy |
| spelling | doaj-art-8bdd2f95e5ca4659a3190b900c43e67f2025-08-20T04:03:07ZengNature Publishing GroupSignal Transduction and Targeted Therapy2059-36352025-07-0110113910.1038/s41392-025-02270-3Nuclear receptors in health and disease: signaling pathways, biological functions and pharmaceutical interventionsPing Jin0Xirui Duan1Zhao Huang2Yuan Dong3Jianmei Zhu4Huiming Guo5Hui Tian6Cheng-Gang Zou7Ke Xie8State 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 UniversityDepartment of Oncology, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine; Shanghai Key Laboratory of Gastric NeoplasmsWest China Institute of Preventive and Medical Integration for Major Diseases, West China School of Public Health and West China Fourth Hospital, Sichuan UniversityDepartment of Breast Surgery, the First Affiliated Hospital of Kunming Medical UniversityDepartment of oncology, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of ChinaDepartment of Gynecology, the First Affiliated Hospital of Kunming Medical UniversityDepartment of Radiation Oncology, the First Affiliated Hospital of Kunming Medical UniversityState 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 UniversityDepartment of oncology, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of ChinaAbstract 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.https://doi.org/10.1038/s41392-025-02270-3 |
| spellingShingle | Ping Jin Xirui Duan Zhao Huang Yuan Dong Jianmei Zhu Huiming Guo Hui Tian Cheng-Gang Zou Ke Xie Nuclear receptors in health and disease: signaling pathways, biological functions and pharmaceutical interventions Signal Transduction and Targeted Therapy |
| title | Nuclear receptors in health and disease: signaling pathways, biological functions and pharmaceutical interventions |
| title_full | Nuclear receptors in health and disease: signaling pathways, biological functions and pharmaceutical interventions |
| title_fullStr | Nuclear receptors in health and disease: signaling pathways, biological functions and pharmaceutical interventions |
| title_full_unstemmed | Nuclear receptors in health and disease: signaling pathways, biological functions and pharmaceutical interventions |
| title_short | Nuclear receptors in health and disease: signaling pathways, biological functions and pharmaceutical interventions |
| title_sort | nuclear receptors in health and disease signaling pathways biological functions and pharmaceutical interventions |
| url | https://doi.org/10.1038/s41392-025-02270-3 |
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