ArticleAging cell2021
Non-genomic rewiring of vitamin D receptor to p53 as a key to Alzheimer's disease.
Article in Aging cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 17 citations in OpenAlex.
- Herbal Formula AC591 Protects Against Cisplatin-Induced Hearing Loss by Inhibiting p53-Mediated Ferroptosis.Smart medicine · 2026Article
- Association between vitamin D supplement use and cognitive functioning: a longitudinal cohort study.BMJ open · 2026Article
- Disrupted Vitamin D Signaling and Metabolism in Neurodevelopmental and Neurodegenerative Disorders.ASN neuro · 2026Review
- Rethinking on bile acid-brain axis: decoding neurotoxic and neuroprotective landscape in aging and Alzheimer's disease.Biogerontology · 2026Review
- Sex- and APOE Genotype-Dependent Pain Susceptibility and Alzheimer's Risk Mediated by the Lipid Metabolism Enzyme LPCAT2.Aging cell · 2025Article
- Neuroprotective Roles of Vitamin D: Bridging the Gap Between Mechanisms and Clinical Applications in Cognitive Decline.International journal of molecular sciences · 2025Review
- From Gut to Brain: Uncovering Potential Serum Biomarkers Connecting Inflammatory Bowel Diseases to Neurodegenerative Diseases.International journal of molecular sciences · 2024Review
- Is There a Role of Vitamin D in Alzheimer's Disease?CNS & neurological disorders drug targets · 2024Review
- Review
- Role of Vitamin D Deficiency in the Pathogenesis of Cardiovascular and Cerebrovascular Diseases.Nutrients · 2023Review
- Association between Low Vitamin D Status, Serotonin, and Clinico-Biobehavioral Parameters in Alzheimer's Disease.Dementia and geriatric cognitive disorders · 2023Article
- Vitamin D supplementation worsens Alzheimer's progression: Animal model and human cohort studies.Aging cell · 2022Article
- Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Observational epidemiological studies have associated vitamin D deficiency with Alzheimer's disease (AD). However, whether vitamin D deficiency would result in some impacts on the vitamin D binding receptor (VDR) remains to be characterized in AD. Vitamin D helps maintain adult brain health genomically through binding with and activating a VDR/retinoid X receptor (RXR) transcriptional complex. Thus, we investigated the role of VDR in AD using postmortem human brains, APP/PS1 mice, and cell cultures. Intriguingly, although vitamin D was decreased in AD patients and mice, hippocampal VDR levels were inversely increased. The abnormally increased levels of VDR were found to be colocalized with Aβ plaques, gliosis and autophagosomes, implicating a non-genomic activation of VDR in AD pathogenesis. Mechanistic investigation revealed that Aβ upregulated VDR without its canonical ligand vitamin D and switched its heterodimer binding-partner from RXR to p53. The VDR/p53 complex localized mostly in the cytosol, increased neuronal autophagy and apoptosis. Chemically inhibiting p53 switched VDR back to RXR, reversing amyloidosis and cognitive impairment in AD mice. These results suggest a non-genomic rewiring of VDR to p53 is key for the progression of AD, and thus VDR/p53 pathway might be targeted to treat people with AD.
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