AI Article Synopsis
- Nuclear hormone receptors (NHRs) are vital transcription factors influenced by ligands from metabolism or diet, making them potential pharmacological targets for health and disease.
- Recent studies highlight the identification of natural ligands for NHRs and propose new evolutionary models for how these ligands interact with receptors, influencing gene regulation.
- The text also addresses the challenges in discovering ligands for the remaining orphan NHRs and suggests innovative methods to uncover these natural ligands.
Article Abstract
Nuclear hormone receptors (NHRs) are a family of ligand-regulated transcription factors that control key aspects of development and physiology. The regulation of NHRs by ligands derived from metabolism or diet makes them excellent pharmacological targets, and the mechanistic understanding of how NHRs interact with their ligands to regulate downstream gene networks, along with the identification of ligands for orphan NHRs, could enable innovative approaches for cellular engineering, disease modeling and regenerative medicine. We review recent discoveries in the identification of physiologic ligands for NHRs. We propose new models of ligand-receptor co-evolution, the emergence of hormonal function and models of regulation of NHR specificity and activity via one-ligand and two-ligand models as well as feedback loops. Lastly, we discuss limitations on the processes for the identification of physiologic NHR ligands and emerging new methodologies that could be used to identify the natural ligands for the remaining 17 orphan NHRs in the human genome.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11311682 | PMC |
| http://dx.doi.org/10.3390/cells13151284 | DOI Listing |
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