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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 PDFClinical implications of mineralocorticoid receptor overactivation.
Clin Kidney J
January 2025
Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
The mineralocorticoid receptor (MR) is a nuclear transcription factor that plays a critical role in regulating fluid, electrolytes, blood pressure, and hemodynamic stability. In conditions such as chronic kidney disease (CKD) and heart failure (HF), MR overactivation leads to increased salt and water retention, inflammatory and fibrotic gene expression, and organ injury. The MR is essential for transcriptional regulation and is implicated in metabolic, proinflammatory, and pro-fibrotic pathways.
View Article and Find Full Text PDFEvolution of mineralocorticoid receptor antagonists, aldosterone synthase inhibitors, and alternative treatments for managing primary aldosteronism.
Hypertens Res
November 2024
Department of Endocrinology, Metabolism, Rheumatology and Nephrology, Faculty of Medicine, Oita University, Oita, Japan.
Primary aldosteronism (PA) is a prevalent and curable secondary hypertensive disorder that accounts for 5-13% of all hypertension cases. The prevalence of resistant hypertension, cerebral and cardiovascular diseases, and renal complications is higher in PA patients than in those with essential hypertension. Appropriate diagnosis and treatment at an early stage may suppress cerebral and cardiovascular events.
View Article and Find Full Text PDFEvaluation of N-palmitoylethanolamine (PEA) binding to nuclear receptors through docking and molecular dynamics studies.
Comput Biol Med
January 2025
Laboratory of Molecular and Cellular Screening Processes, Centre of Biotechnology of Sfax, University of Sfax, P O Box 1177, Sidi Mansour Road, 3018, Sfax, Tunisia.
N-palmitoylethanolamine (PEA) is an endogenous bioactive compound recognized for its anti-inflammatory effects and its role in tissue protection and repair. Despite the proposal of peroxisome proliferator-activated receptor alpha (PPARα) as a potential receptor for PEA, direct evidence of binding remains insufficient. This study offers a comprehensive analysis of human nuclear receptors (NRs) through structural bioinformatics and molecular docking, evaluating a total of 367 unique NR structures across 47 subfamilies.
View Article and Find Full Text PDFThe glucocorticoid receptor potentiates aldosterone-induced transcription by the mineralocorticoid receptor.
Proc Natl Acad Sci U S A
November 2024
Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, NIH, Bethesda, MD 20892.
The glucocorticoid and mineralocorticoid receptors (GR and MR, respectively) have distinct, yet overlapping physiological and pathophysiological functions. There are indications that both receptors interact functionally and physically, but the precise role of this interdependence is poorly understood. Here, we analyzed the impact of GR coexpression on MR genome-wide transcriptional responses and chromatin binding upon activation by aldosterone and glucocorticoids, both physiological ligands of this receptor.
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