ArticleEMBO reports2014
sAPP modulates iron efflux from brain microvascular endothelial cells by stabilizing the ferrous iron exporter ferroportin.
Article in EMBO reports, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
79 citing papers in PubMed, 107 citations in OpenAlex.
- Ferroportin at the Crossroads of Iron Biology: Disease, Regulation and Modulation.Biomolecules · 2026Review
- How does iron cross the abluminal membrane of the blood-brain barrier.Experimental & molecular medicine · 2026Review
- Amyloid Precursor Protein Abnormalities Destabilize Membrane Ferroportin: A Novel Mechanism Underlying Early Brain Pathologies and Memory Impairment in Alzheimer's Disease.International journal of molecular sciences · 2026Article
- Iron toxicity potentiates cell-type specific amyloid beta proteotoxicity inbioRxiv : the preprint server for biology · 2026Article
- Reexamining the Role of Amyloid β Clearance from the Brain: Exporting Labile Iron from the Interstitial Fluid Performs a Protective Function.International journal of molecular sciences · 2026Review
- The Crosstalk Between Ferritinophagy and Ferroptosis in Ischemic Stroke: Regulatory Mechanisms and Therapeutic Implications.Cellular and molecular neurobiology · 2025Review
- Iron-Mediated Overexpression of Amyloid Precursor Protein via Iron Responsive mRNA in Alzheimer's Disease.International journal of molecular sciences · 2025Review
- Genetic Markers of Postmortem Brain Iron.Journal of neurochemistry · 2025Article
- Ferroptosis: a novel pathogenesis and therapeutic strategies for Parkinson disease: A review.Medicine · 2025Review
- Iron responsive elements mRNA regulate Alzheimer's amyloid precursor protein translation through iron sensing.Frontiers in aging neuroscience · 2025Review
- Targeting Iron Responsive Elements (IREs) of APP mRNA into Novel Therapeutics to Control the Translation of Amyloid-β Precursor Protein in Alzheimer's Disease.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Mechanism of ferroptosis regulating ischemic stroke and pharmacologically inhibiting ferroptosis in treatment of ischemic stroke.CNS neuroscience & therapeutics · 2024Review
- Brain Iron Dyshomeostasis and Ferroptosis in Alzheimer's Disease Pathophysiology: Two Faces of the Same Coin.Aging and disease · 2024Review
- The Irony of Iron: The Element with Diverse Influence on Neurodegenerative Diseases.International journal of molecular sciences · 2024Review
- Iron imbalance in neurodegeneration.Molecular psychiatry · 2024Review
- Ferroptosis regulation through Nrf2 and implications for neurodegenerative diseases.Archives of toxicology · 2024Review
- Iron Overload in Brain: Transport Mismatches, Microbleeding Events, and How Nanochelating Therapies May Counteract Their Effects.International journal of molecular sciences · 2024Review
- 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
- Review
- Loss of filamentous actin, tight junction protein expression, and paracellular barrier integrity in frataxin-deficient human brain microvascular endothelial cells-implications for blood-brain barrier physiology in Friedreich's ataxia.Frontiers in molecular biosciences · 2023Article
19 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
A sequence within the E2 domain of soluble amyloid precursor protein (sAPP) stimulates iron efflux. This activity has been attributed to a ferroxidase activity suggested for this motif. We demonstrate that the stimulation of efflux supported by this peptide and by sAPPα is due to their stabilization of the ferrous iron exporter, ferroportin (Fpn), in the plasma membrane of human brain microvascular endothelial cells (hBMVEC). The peptide does not bind ferric iron explaining why it does not and thermodynamically cannot promote ferrous iron autoxidation. This peptide specifically pulls Fpn down from the plasma membrane of hBMVEC; based on these results, FTP, for ferroportin-targeting peptide, correctly identifies the function of this peptide. The data suggest that in stabilizing Fpn via the targeting due to the FTP sequence, sAPP will increase the flux of iron into the cerebral interstitium. This inference correlates with the observation of significant iron deposition in the amyloid plaques characteristic of Alzheimer's disease.
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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.