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Advances in Molecular Research of Nuclear Receptors in Disease

A Special Issue of International Journal of Molecular Sciences (ISSN 1422-0067) belonging to the section "Biochemistry".

Deadline for manuscript submissions: closed (20 October 2025) | Viewed by 2974

Editor


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Guest Editor
Faculty of Pharmacy, Iryo Sosei University, Iwaki, Fukushima 970-8044, Japan
Interests: regulation of gene expression and epigenetics by steroid hormones; bone biology; genome medicine in cancer

Special Issue Information

Dear Colleagues,

Nuclear receptors for steroid/thyroid hormones and fat-soluble vitamins play key roles in a wide variety of physiological events and facilitate processes of pathological events. Especially, in hormone-dependent tumors found in breast and prostate cancer patients, the significance of sex hormone receptors is widely accepted from bench-to-bed-side sciences. Pharmacologically, synthetic estrogens have been clinically successful to mitigate bone health impaired in osteoporotic patients. Alongside these diseases, other chronic diseases appear to be under the influence and control of nuclear receptor functions, but the molecular basis for the role of nuclear receptors largely remains elusive. In this Special Issue, any aspect of the current progress in medical research for nuclear receptor function and their ligands at molecular levels is welcome to update readers on nuclear receptor research.

Dr. Shigeaki Kato
Guest Editor

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Keywords

  • nuclear receptors
  • steroid hormones
  • fat-soluble vitamins
  • cancer
  • non-communicable diseases
  • synthetic ligands

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Published Papers (1 paper)

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Review

24 pages, 3147 KB  
Review
Vitamin D Receptor Signaling and Ligand Modulation: Molecular Mechanisms and Therapeutic Implications
by Tram Thi-Ngoc Nguyen, Kouki Nojiri, Tomohiro Kurokawa, Takahiro Sawada, Yoshiaki Kanemoto and Shigeaki Kato
Int. J. Mol. Sci. 2026, 27(5), 2396; https://doi.org/10.3390/ijms27052396 - 4 Mar 2026
Cited by 7 | Viewed by 2242
Abstract
Vitamin D, a fat-soluble vitamin functioning as a hormone via the vitamin D receptor (VDR), is critical for calcium homeostasis and bone health. Vitamin D deficiency is linked to nutritional rickets, osteomalacia, and increased risk of non-communicable diseases such as cancer and diabetes. [...] Read more.
Vitamin D, a fat-soluble vitamin functioning as a hormone via the vitamin D receptor (VDR), is critical for calcium homeostasis and bone health. Vitamin D deficiency is linked to nutritional rickets, osteomalacia, and increased risk of non-communicable diseases such as cancer and diabetes. While serum 25(OH)D3 is used to assess vitamin D status, its active form, 1α,25(OH)2D3, exerts context-dependent effects on calcium metabolism. Nonetheless, the therapeutic utility of native vitamin D is limited in certain pathologies. In chronic kidney disease (CKD), the renal conversion of 25(OH)D3 to active 1α,25(OH)2D3 is compromised, necessitating the use of active synthetic analogs to bypass this metabolic defect. Furthermore, for dermatological and oncological disorders requiring supraphysiological dosing, synthetic analogs have been designed to dissociate beneficial anti-proliferative effects from the severe hypercalcemia induced by high-dose 1α,25(OH)2D3. VDR mediates transcriptional responses, modulated by co-regulators and chromatin remodeling complexes. Recent discoveries include non-genomic VDR pathways and SCAP (SREBP cleavage-activating protein)-dependent signaling that modulate lipid metabolism. Despite promising preclinical results, most synthetic VDR agonists fail to show efficacy in cancer therapy due to calcemic toxicity. However, compounds like eldecalcitol are effective in osteoporosis, especially in low-calcium-intake populations. Selective VDR modulators, akin to SERMs, exhibit tissue-specific effects. Moreover, novel VDR antagonists such as ZK168281 demonstrate potential to suppress hypercalcemia and vitamin D toxicity by inhibiting transcriptional activity and altering VDR localization. These agents may enable anti-inflammatory or anti-proliferative actions without calcemic risks. Understanding the nuanced biology of vitamin D and its analogs offers new avenues for therapeutic intervention beyond bone metabolism, including managing hyperparathyroidism, granulomatous diseases, and inflammation-associated disorders. Full article
(This article belongs to the Special Issue Advances in Molecular Research of Nuclear Receptors in Disease)
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