ArticleCellular and molecular neurobiology2018
The Ferroxidase Hephaestin But Not Amyloid Precursor Protein is Required for Ferroportin-Supported Iron Efflux in Primary Hippocampal Neurons.
Article in Cellular and molecular neurobiology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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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
28 citing papers in PubMed, 49 citations in OpenAlex.
- Iron Supplementation and Copper Homeostasis: Evidence for Potential Copper Depletion, Biomarker Challenges, and Clinical Implications.Nutrients · 2026Review
- Exploring and Targeting the Connection of Iron and Copper Homeostasis to Neurodegenerative Diseases.MedComm · 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
- 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
- Role of iron in brain development, aging, and neurodegenerative diseases.Annals of medicine · 2025Review
- Stress-Induced Dysregulation of Brain Iron Metabolism and Its Links to Neurological Disorders.Biology · 2025Review
- The Ferroxidase-Permease System for Transport of Iron Across Membranes: From Yeast to Humans.International journal of molecular sciences · 2025Review
- Mammalian copper homeostasis: physiological roles and molecular mechanisms.Physiological reviews · 2025Review
- Gut to brain: essential micronutrient and trace element manganese transport, function and toxicity.Frontiers in physiology · 2025Review
- Peroxynitrite-Triggered Carbon Monoxide Donor Improves Ischemic Stroke Outcome by Inhibiting Neuronal Apoptosis and Ferroptosis.Molecular neurobiology · 2024Article
- Review
- Apo- and holo-transferrin differentially interact with hephaestin and ferroportin in a novel mechanism of cellular iron release regulation.Journal of biomedical science · 2023Article
- The biology of mammalian multi-copper ferroxidases.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
- The divergent effects of astrocyte ceruloplasmin on learning and memory function in young and old mice.Cell death & disease · 2022Article
- Role of endolysosome function in iron metabolism and brain carcinogenesis.Seminars in cancer biology · 2021Review
- Ferroptosis Mechanisms Involved in Hippocampal-Related Diseases.International journal of molecular sciences · 2021Review
- Production of Recombinant Human Ceruloplasmin: Improvements and Perspectives.International journal of molecular sciences · 2021Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Iron efflux in mammalian cells is mediated by the ferrous iron exporter ferroportin (Fpn); Fpn plasma membrane localization and function are supported by a multicopper ferroxidase and/or the soluble amyloid precursor protein (sAPP). Fpn and APP are ubiquitously expressed in all cell types in the central nervous system including neurons. In contrast, neuronal ferroxidase(s) expression has not been well characterized. Using primary cultures of hippocampal neurons, we examined the molecular mechanism of neuronal Fe efflux in detail. Developmental increases of Fpn, APP, and the ferroxidase hephaestin (Hp) were observed in hippocampal neurons. Iron efflux in these neurons depended on the level of Fpn localized at the cell surface; as noted, Fpn stability is supported by ferroxidase activity, an enzymatic activity that is required for Fe efflux. Iron accumulation increases and iron efflux decreases in Hp knockout neurons. In contrast, suppression of endogenous APP by RNAi knockdown does not affect surface Fpn stability or Fe efflux. These data support the model that the neuronal ferroxidase Hp plays a unique role in support of Fpn-mediated Fe efflux in primary hippocampal neurons. Our data also demonstrate that Hp ferroxidase activity relies on copper bioavailability, which suggests neuronal iron homeostasis will be modulated by cellular copper status.
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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.