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Leveraging nuclear receptor mediated transcriptional signaling for drug discovery: Historical insights and current advances.
Adv Protein Chem Struct Biol
January 2025
Department of Life Sciences, Kristu Jayanti College, Autonomous, Bengaluru, Karnataka, India. Electronic address:
Nuclear receptors (NRs) are ligand-activated transcription factors that regulate gene expression in response to physiological signals, such as hormones and other chemical messengers. These receptors either activate or repress the transcription of target genes, which in turn promotes or suppresses physiological processes governing growth, differentiation, and homeostasis. NRs bind to specific DNA sequences and, in response to ligand binding, either promote or hinder the assembly of the transcriptional machinery, thereby influencing gene expression at the transcriptional level.
View Article and Find Full Text PDFComparative glucocorticoid receptor agonism: In silico, in vitro, and in vivo and identification of potential biomarkers for synthetic glucocorticoid exposure.
Environ Toxicol Chem
January 2025
Department of Environmental Science, Center for Reservoir and Aquatic Systems Research, Baylor University, Waco, TX, United States.
The glucocorticoid receptor (GR) is present in almost every vertebrate cell and is utilized in many biological processes. Despite an abundance of mammalian data, the structural conservation of the receptor and cross-species susceptibility, particularly for aquatic species, has not been well defined. Efforts to reduce, refine, and/or replace animal testing have increased, driving the impetus to advance development of new approach methodologies (NAMs).
View Article and Find Full Text PDFFKBP51 overexpression in the corticolimbic system stabilizes circadian rhythms.
Cell Stress Chaperones
December 2024
Byrd Alzheimer's Center and Research Institute, Tampa, FL 33613, USA; Department of Molecular Medicine, University of South Florida, Tampa, FL 33612, USA; Research and Development, James A. Haley Veterans Hospital, Tampa, FL 33612, USA. Electronic address:
Circadian rhythm disruptions have been associated with a wide range of health issues and complications, including an increased risk of circadian rhythm sleep disorders (CRSDs). CRSDs are common among individuals who have been through a traumatic event, particularly in those who have post-traumatic stress disorder (PTSD). Allelic variations in the gene encoding for FK506-binding protein 51 (FKBP51) can increase the susceptibility for PTSD and other stress-related disorders following trauma.
View Article and Find Full Text PDFMicrovesicle-Shuttled microRNA-130b Activates the Hepatic Inflammation by Inhibiting Glucocorticoid-Receptor-Mediated Immunosuppression in High-Fat Diet-Induced Obese Mice.
Vet Sci
November 2024
College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China.
Article Synopsis
- Metabolism-disorder-induced liver diseases are rising globally, linked to obesity and type 2 diabetes, with plasma miR-130b emerging as a key biomarker for early diagnosis and treatment.
- A study on high-fat diet-induced obese mice showed that injecting miR-130b-MV significantly reduced body weight but increased liver weight ratio while also activating hepatic inflammation by enhancing proinflammatory gene expression.
- The findings indicate that miR-130b-MV promotes liver inflammation by inhibiting GR-mediated immunosuppression, revealing a new mechanism related to metabolic disorders.
Transcriptome-wide analysis for glucocorticoid receptor-mediated mRNA decay reveals various classes of target transcripts.
Mol Cells
November 2024
Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea. Electronic address:
The glucocorticoid receptor (GR) can bind to DNA or RNA, eliciting transcriptional activation/repression or rapid messenger RNA (mRNA) degradation, respectively. Although GR-mediated transcriptional regulation has been well-characterized, the molecular details of rapid mRNA degradation induced by glucocorticoids are not yet fully understood. Here, we demonstrate that glucocorticoid-induced GR-mediated mRNA decay (GMD) takes place in the nucleus and the cytoplasm, acting on pre-mRNAs and mRNAs.
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