The role of nuclear receptors in metabolic homeostasis and disease: From molecular mechanisms to drug discovery
Nuclear receptors (NRs) are a superfamily of ligand-dependent transcription factors that serve as pivotal regulators of gene expression in response to hormonal, metabolic, and environmental cues. They exert transcriptional control through complex interactions with co-regulators, thereby influencing...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-08-01
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| Series: | Pharmacological Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1043661825002816 |
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| author | Fangfang He Haomeng Wu Feilong Zhao Xinxin Liu Qin Yang Shiquan Zhou Tianling Xu Jing Xu Shuai Wang Denglang Zou |
| author_facet | Fangfang He Haomeng Wu Feilong Zhao Xinxin Liu Qin Yang Shiquan Zhou Tianling Xu Jing Xu Shuai Wang Denglang Zou |
| author_sort | Fangfang He |
| collection | DOAJ |
| description | Nuclear receptors (NRs) are a superfamily of ligand-dependent transcription factors that serve as pivotal regulators of gene expression in response to hormonal, metabolic, and environmental cues. They exert transcriptional control through complex interactions with co-regulators, thereby influencing gene networks involved in metabolic regulation, cell signaling, immune modulation, and homeostatic maintenance. Dysregulation of NR activity has been implicated in the pathogenesis of various metabolic and inflammatory conditions through altered gene expression and signaling cascades. This review provides an integrated overview of NR structural features and classification, elucidates their mechanisms of action in gene regulation and metabolic balance, and explores their dual roles in both physiological and pathological contexts. We further examine recent advances in NR-targeted drug discovery, including structure-based drug design, chemical biology approaches, and AI-assisted ligand development. Finally, we highlight multidisciplinary perspectives and emerging directions for NR research within the framework of precision medicine. |
| format | Article |
| id | doaj-art-41ba98e3885046c394dfed1c59207c7d |
| institution | DOAJ |
| issn | 1096-1186 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Pharmacological Research |
| spelling | doaj-art-41ba98e3885046c394dfed1c59207c7d2025-08-20T02:45:42ZengElsevierPharmacological Research1096-11862025-08-0121810785610.1016/j.phrs.2025.107856The role of nuclear receptors in metabolic homeostasis and disease: From molecular mechanisms to drug discoveryFangfang He0Haomeng Wu1Feilong Zhao2Xinxin Liu3Qin Yang4Shiquan Zhou5Tianling Xu6Jing Xu7Shuai Wang8Denglang Zou9College of Pharmacy, Hubei University of Chinese Medicine, Wuhan, China; Hubei Shizhen Laboratory, Hubei University of Chinese Medicine, Wuhan, ChinaThe Second Affiliated Hospital of Guangzhou University of Chinese Medicine, State Key Laboratory of Traditional Chinese Medicine Syndrome, State Key Laboratory of Dampness Syndrome of Chinese Medicine, Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, ChinaCollege of Pharmacy, Hubei University of Chinese Medicine, Wuhan, China; Hubei Shizhen Laboratory, Hubei University of Chinese Medicine, Wuhan, ChinaCollege of Pharmacy, Hubei University of Chinese Medicine, Wuhan, China; Hubei Shizhen Laboratory, Hubei University of Chinese Medicine, Wuhan, ChinaCollege of Pharmacy, Hubei University of Chinese Medicine, Wuhan, China; Hubei Shizhen Laboratory, Hubei University of Chinese Medicine, Wuhan, ChinaCollege of Pharmacy, Hubei University of Chinese Medicine, Wuhan, China; Hubei Shizhen Laboratory, Hubei University of Chinese Medicine, Wuhan, ChinaCollege of Pharmacy, Hubei University of Chinese Medicine, Wuhan, China; Hubei Shizhen Laboratory, Hubei University of Chinese Medicine, Wuhan, ChinaCollege of Pharmacy, Hubei University of Chinese Medicine, Wuhan, China; Hubei Shizhen Laboratory, Hubei University of Chinese Medicine, Wuhan, ChinaState Key Laboratory of Traditional Chinese Medicine Syndrome, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China; Chinese Medicine Guangdong Laboratory, Hengqin, China; Corresponding author at: State Key Laboratory of Traditional Chinese Medicine Syndrome, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China.College of Pharmacy, Hubei University of Chinese Medicine, Wuhan, China; Hubei Shizhen Laboratory, Hubei University of Chinese Medicine, Wuhan, China; Corresponding author at: College of Pharmacy, Hubei University of Chinese Medicine, Wuhan, China.Nuclear receptors (NRs) are a superfamily of ligand-dependent transcription factors that serve as pivotal regulators of gene expression in response to hormonal, metabolic, and environmental cues. They exert transcriptional control through complex interactions with co-regulators, thereby influencing gene networks involved in metabolic regulation, cell signaling, immune modulation, and homeostatic maintenance. Dysregulation of NR activity has been implicated in the pathogenesis of various metabolic and inflammatory conditions through altered gene expression and signaling cascades. This review provides an integrated overview of NR structural features and classification, elucidates their mechanisms of action in gene regulation and metabolic balance, and explores their dual roles in both physiological and pathological contexts. We further examine recent advances in NR-targeted drug discovery, including structure-based drug design, chemical biology approaches, and AI-assisted ligand development. Finally, we highlight multidisciplinary perspectives and emerging directions for NR research within the framework of precision medicine.http://www.sciencedirect.com/science/article/pii/S1043661825002816Nuclear receptorMetabolismDiseaseDrug developmentPharmacology |
| spellingShingle | Fangfang He Haomeng Wu Feilong Zhao Xinxin Liu Qin Yang Shiquan Zhou Tianling Xu Jing Xu Shuai Wang Denglang Zou The role of nuclear receptors in metabolic homeostasis and disease: From molecular mechanisms to drug discovery Pharmacological Research Nuclear receptor Metabolism Disease Drug development Pharmacology |
| title | The role of nuclear receptors in metabolic homeostasis and disease: From molecular mechanisms to drug discovery |
| title_full | The role of nuclear receptors in metabolic homeostasis and disease: From molecular mechanisms to drug discovery |
| title_fullStr | The role of nuclear receptors in metabolic homeostasis and disease: From molecular mechanisms to drug discovery |
| title_full_unstemmed | The role of nuclear receptors in metabolic homeostasis and disease: From molecular mechanisms to drug discovery |
| title_short | The role of nuclear receptors in metabolic homeostasis and disease: From molecular mechanisms to drug discovery |
| title_sort | role of nuclear receptors in metabolic homeostasis and disease from molecular mechanisms to drug discovery |
| topic | Nuclear receptor Metabolism Disease Drug development Pharmacology |
| url | http://www.sciencedirect.com/science/article/pii/S1043661825002816 |
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