ArticleCell death & disease2022
Astrocyte-derived hepcidin controls iron traffic at the blood-brain-barrier via regulating ferroportin 1 of microvascular endothelial cells.
Article in Cell death & disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
57 citing papers in PubMed, 77 citations in OpenAlex.
- Rescuing anxiety by targeting the neuronal-astrocytic iron signaling axis in male mice.Signal transduction and targeted therapy · 2026Article
- Convergent Astrocytic Failure in Parkinson's Disease: A System-Level Model of Pathogenesis and Treatment.Molecular neurobiology · 2026Review
- Iron dyshomeostasis and its neurobiological mechanisms in psychiatric disorders.Molecular psychiatry · 2026Review
- Exercise and Ferroptosis in Neurodegenerative Diseases: Direct Evidence, Mechanistic Links, and Translational Gaps.International journal of molecular sciences · 2026Review
- From Iron to Depression: The Crosstalk Between the Periphery and Brain.Neuroscience bulletin · 2026Review
- How does iron cross the abluminal membrane of the blood-brain barrier.Experimental & molecular medicine · 2026Review
- Review
- Serum Biomarkers in Restless Legs Syndrome: Beyond the Classical Iron Paradigm-A Scoping Review.International journal of molecular sciences · 2026Article
- Sex and Diet Biased Effect of L-DOPA on Iron Accumulation in the Ventral Midbrain.Journal of neurochemistry · 2026Article
- Targeting Ferroptosis for Cerebral Neuroprotection in Ischemic Stroke: Pathophysiological Insights.International journal of general medicine · 2026Review
- Single-cell RNA-seq reveals the piperlongumine is a potential drug for ischemic stroke.PloS one · 2026Article
- Ferroptosis: an emerging key mechanism linking aging, surgical and anesthetic exposure to postoperative cognitive dysfunction.Frontiers in immunology · 2026Review
- Iron-driven secondary injury after intracranial hemorrhage: mitochondrial dysfunction and ferroptosis.Frontiers in neuroscience · 2026Review
- Metabolic Regulatory Networks in Ferroptosis During Alzheimer's Disease, Mechanisms of Glial Cell Action, and Pathological Correlations with Neuritic Plaques.International journal of general medicine · 2026Review
- From scavenger to victim: mechanism and treatment of microglial ferroptosis in white matter injury disease.Frontiers in immunology · 2026Review
- Multidimensional iron dysmetabolism and gut-brain axis interactions in restless legs syndrome: from peripheral deficiency to central dysregulation.Frontiers in aging neuroscience · 2026Review
- Iron dyshomeostasis in neuropsychiatric disorders.Frontiers in psychiatry · 2026Review
- Ferroptosis in microglial activation: a systematic review and multidata comparison.Brain communications · 2026Review
- Labile iron overload reprograms microglia and neurons for lipid droplet synthesis in the aging brain.bioRxiv : the preprint server for biology · 2025Article
- The role of microglia in neurodegenerative diseases: from the perspective of ferroptosis.Acta pharmacologica Sinica · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Brain iron dysregulation associated with aging is closely related to motor and cognitive impairments in neurodegenerative diseases. The regulation of iron traffic at the blood-brain barrier (BBB) is crucial to maintain brain iron homeostasis. However, the specific mechanism has not been clarified in detail. Using various conditional gene knockout and overexpression mice, as well as cell co-culture of astrocyte and bEND.3 in the transwell, we found that astrocyte hepcidin knockdown increased the expression of ferroportin 1 (FPN1) of brain microvascular endothelial cells (BMVECs), and that it also induced brain iron overload and cognitive decline in mice. Moreover, BMVECs FPN1 knockout decreased iron contents in the cortex and hippocampus. Furthermore, hepcidin regulates the level of FPN1 of BMVECs with conditional gene overexpression in vivo and in vitro. Our results revealed that astrocytes responded to the intracellular high iron level and increased the secretion of hepcidin, which in turn diminished iron uptake at BBB from circulation through directly regulating FPN1 of BMVECs. Our results demonstrate that FPN1 of BMVECs is a gateway for iron transport into the brain from circulation, and the controller of this gateway is hepcidin secreted by astrocyte at its endfeet through physical contact with BMVECs. This regulation is indeed the major checkpoint for iron transport from the blood circulation to the brain. This study delineates the pathway and regulation of iron entry into the brain, providing potential therapeutic targets for iron dysregulation-related neurological diseases.
Indexed as
Identifiers
What OpenQuestion holds
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.