ArticleJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism2015
A novel model for brain iron uptake: introducing the concept of regulation.
Article in Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers, 1 of them a synthesis that pooled it.
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The trial behind it
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Who cites it
80 citing papers in PubMed, 1 synthesis or guideline pooled it, 144 citations in OpenAlex.
- Age and sex-based impacts of maternal iron deficiency on offspring's cognitive function and anemia: A systematic review.European journal of clinical nutrition · 2024Pooled it
- Changes in Iron Status Are Related to Changes in Brain Activity and Behavior in Rwandan Female University Students: Results from a Randomized Controlled Efficacy Trial Involving Iron-Biofortified Beans.The Journal of nutrition · 2019Trial
- Postnatal Iron Supplementation Fails to Fully Rescue Brain Metal and Transcriptional Defects Caused by Nutrition-Based Gestational Iron Deficiency.The Journal of nutrition · 2026Article
- Cerebrospinal Fluid from Restless Legs Syndrome Patients Reduces Iron Uptake in Blood-Brain Barrier Endothelial Cells by Disrupting the Regulation of Transferrin Receptors.Annals of neurology · 2026Article
- How does iron cross the abluminal membrane of the blood-brain barrier.Experimental & molecular medicine · 2026Review
- Regulation of brain iron homeostasis and its influence on cognitive function.European radiology · 2026Article
- L-DOPA influences transferrin-dependent iron release at the blood-brain barrier.Fluids and barriers of the CNS · 2026Article
- Serotransferrin enhances transferrin receptor-mediated brain uptake of antibodies.Drug delivery and translational research · 2025Article
- Astrocyte secretome remodeling under iron deficiency: potential implications for brain iron homeostasis.Biology open · 2025Article
- Homeostasis and metabolism of iron and other metal ions in neurodegenerative diseases.Signal transduction and targeted therapy · 2025Review
- Iron imbalance in neurodegeneration.Molecular psychiatry · 2024Review
- Ferroptosis regulation through Nrf2 and implications for neurodegenerative diseases.Archives of toxicology · 2024Review
- Brain Iron Homeostasis and Mental Disorders.Antioxidants (Basel, Switzerland) · 2023Review
- Amyloid-β exposed astrocytes induce iron transport from endothelial cells at the blood-brain barrier by altering the ratio of apo- and holo-transferrin.Journal of neurochemistry · 2023Article
- A novel view of ferritin in cancer.Biochimica et biophysica acta. Reviews on cancer · 2023Review
- Apo- and holo-transferrin differentially interact with hephaestin and ferroportin in a novel mechanism of cellular iron release regulation.Journal of biomedical science · 2023Article
- Iron and Ferroptosis More than a Suspect: Beyond the Most Common Mechanisms of Neurodegeneration for New Therapeutic Approaches to Cognitive Decline and Dementia.International journal of molecular sciences · 2023Review
- Lactoferrin: from the structure to the functional orchestration of iron homeostasis.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2023Review
- Apo- and holo- transferrin differentially interact with ferroportin and hephaestin to regulate iron release at the blood-brain barrier.Research square · 2023Article
- Apo- and holo- transferrin differentially interact with ferroportin and hephaestin to regulate iron release at the blood-brain barrier.bioRxiv : the preprint server for biology · 2023Article
20 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Neurologic disorders such as Alzheimer's, Parkinson's disease, and Restless Legs Syndrome involve a loss of brain iron homeostasis. Moreover, iron deficiency is the most prevalent nutritional concern worldwide with many associated cognitive and neural ramifications. Therefore, understanding the mechanisms by which iron enters the brain and how those processes are regulated addresses significant global health issues. The existing paradigm assumes that the endothelial cells (ECs) forming the blood-brain barrier (BBB) serve as a simple conduit for transport of transferrin-bound iron. This concept is a significant oversimplification, at minimum failing to account for the iron needs of the ECs. Using an in vivo model of brain iron deficiency, the Belgrade rat, we show the distribution of transferrin receptors in brain microvasculature is altered in luminal, intracellular, and abluminal membranes dependent on brain iron status. We used a cell culture model of the BBB to show the presence of factors that influence iron release in non-human primate cerebrospinal fluid and conditioned media from astrocytes; specifically apo-transferrin and hepcidin were found to increase and decrease iron release, respectively. These data have been integrated into an interactive model where BBB ECs are central in the regulation of cerebral iron metabolism.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.