Vitamin D Receptor Signaling and Ligand Modulation: Molecular Mechanisms and Therapeutic Implications - PubMed
5 hours ago
- #Hypercalcemia
- #Vitamin D Receptor
- #Synthetic Analogs
- Vitamin D functions as a hormone via the vitamin D receptor (VDR) and is crucial for calcium homeostasis and bone health.
- Vitamin D deficiency is associated with nutritional rickets, osteomalacia, and increased risk of non-communicable diseases like cancer and diabetes.
- The active form of vitamin D, 1α,25(OH)2D3, has context-dependent effects on calcium metabolism.
- In chronic kidney disease (CKD), synthetic analogs of vitamin D are used due to compromised renal conversion of 25(OH)D3 to active 1α,25(OH)2D3.
- Synthetic analogs are designed to provide therapeutic benefits without inducing severe hypercalcemia, especially in dermatological and oncological disorders.
- VDR mediates transcriptional responses and is modulated by co-regulators and chromatin remodeling complexes.
- Recent discoveries include non-genomic VDR pathways and SCAP-dependent signaling that influence lipid metabolism.
- Most synthetic VDR agonists have limited efficacy in cancer therapy due to calcemic toxicity, but some like eldecalcitol are effective in osteoporosis.
- Selective VDR modulators exhibit tissue-specific effects, similar to SERMs.
- Novel VDR antagonists like ZK168281 show potential in suppressing hypercalcemia and vitamin D toxicity by altering VDR activity and localization.
- Vitamin D and its analogs offer therapeutic potential beyond bone metabolism, including managing hyperparathyroidism, granulomatous diseases, and inflammation-associated disorders.