ArticleMolecular neurodegeneration2016
Vitamin D interacts with Esr1 and Igf1 to regulate molecular pathways relevant to Alzheimer's disease.
Article in Molecular neurodegeneration, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
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Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 75 citations in OpenAlex.
- Natural Compounds for Alzheimer's Disease Therapy: A Systematic Review of Preclinical and Clinical Studies.International journal of molecular sciences · 2019Pooled it
- Reimagining GSK-3β Therapeutics in Alzheimer's Disease: From Inhibition to Activity Normalization and Targeted Degradation.Journal of molecular neuroscience : MN · 2026Review
- Vitamin D Regulates Olfactory Function via Dual Transcriptional and mTOR-Dependent Translational Control of Synaptic Proteins.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Cholecalciferol (vitamin D3) is an agonist of the Alzheimer's disease-associated immune receptor TREM2.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- The relationship between vitamin D levels and depression: a genetically informed study.Nutrition journal · 2025Article
- Unlocking the Potential of Vitamin D: A Comprehensive Exploration of Its Role in Neurological Health and Diseases.Biology · 2025Review
- Crosstalk between bone and brain in Alzheimer's disease: Mechanisms, applications, and perspectives.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Review
- The Potential Role of Vitamin D Supplementation in Cognitive Impairment Prevention.CNS & neurological disorders drug targets · 2024Review
- Neuroinflammation in Alzheimer's disease: potential beneficial effects of vitamin D.Metabolic brain disease · 2023Review
- Review
- There is no evidence that vitamin D supplementation drives the progression of Alzheimer's disease.Aging cell · 2023Article
- The Synaptic and Circuit Functions of Vitamin D in Neurodevelopment Disorders.Neuropsychiatric disease and treatment · 2023Review
- Review
- Association of vitamin D receptor gene haplotypes with late-onset Alzheimer's disease in a Southeastern European Caucasian population.Experimental and therapeutic medicine · 2022Article
- Vitamin D supplementation worsens Alzheimer's progression: Animal model and human cohort studies.Aging cell · 2022Article
- A Set of Dysregulated Target Genes to Reduce Neuroinflammation at Molecular Level.International journal of molecular sciences · 2022Article
- Association of vitamin D receptor gene TaqI polymorphism with Alzheimer's disease in a Southeastern European Caucasian population.Experimental and therapeutic medicine · 2022Article
- Mechanisms Linking Vitamin D Deficiency to Impaired Metabolism: An Overview.International journal of endocrinology · 2022Review
- Chlorpyrifos residue level and ADHD among children aged 1-6 years in rural China: A cross-sectional study.Frontiers in pediatrics · 2022Article
- Vitamin D actions in neurons require the PI3K pathway for both enhancing insulin signaling and rapid depolarizing effects.The Journal of steroid biochemistry and molecular biology · 2020Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIncreasing evidence suggests a potential therapeutic benefit of vitamin D supplementation against Alzheimer's disease (AD). Although studies have shown improvements in cognitive performance and decreases in markers of the pathology after chronic treatment, the mechanisms by which vitamin D acts on brain cells are multiple and remain to be thoroughly studied. We analyzed the molecular changes observed after 5 months of vitamin D3 supplementation in the brains of transgenic 5xFAD (Tg) mice, a recognized mouse model of AD, and their wild type (Wt) littermates. We first performed a kinematic behavioural examination at 4, 6 and 8 months of age (M4, M6 and M8) followed by a histologic assessment of AD markers. We then performed a comparative transcriptomic analysis of mRNA regulation in the neocortex and hippocampus of 9 months old (M9) female mice.
resultsTranscriptomic analysis of the hippocampus and neocortex of both Wt and Tg mice at M9, following 5 months of vitamin D3 treatment, reveals a large panel of dysregulated pathways related to i) immune and inflammatory response, ii) neurotransmitter activity, iii) endothelial and vascular processes and iv) hormonal alterations. The differentially expressed genes are not all direct targets of the vitamin D-VDR pathway and it appears that vitamin D action engages in the crosstalk with estrogen and insulin signaling. The misexpression of the large number of genes observed in this study translates into improved learning and memory performance and a decrease in amyloid plaques and astrogliosis in Tg animals.
conclusionsThis study underlies the multiplicity of action of this potent neurosteroid in an aging and AD-like brain. The classical and non-classical actions of vitamin D3 can act in an additive and possibly synergistic manner to induce neuroprotective activities in a context-specific way.
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