ArticlePharmaceutics2021
Endothelial Iron Homeostasis Regulates Blood-Brain Barrier Integrity via the HIF2α-Ve-Cadherin Pathway.
Article in Pharmaceutics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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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.
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Who cites it
20 citing papers in PubMed, 37 citations in OpenAlex.
- Mitochondrial Protection and Neural Repair via ROS-Responsive Biomimetic Nanoparticles in Intracerebral Hemorrhage.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- αO-Conotoxin GeXIVA[1,2] Attenuates Paclitaxel-Induced Neurotoxicity by Suppressing Ferroptosis via the Nrf2/SLC7A11/GSH/GPX4 Pathway.Marine drugs · 2026Article
- Mechanistic insights into a novel GPX4 inhibitor Compound AI-3p reversing cisplatin-resistance in ovarian cancer cells.Journal of ovarian research · 2026Article
- p23 protects against ferroptosis of brain microvascular endothelial cells in ischemic stroke.International journal of molecular medicine · 2025Article
- Structure and function of the blood-brain barrier in perioperative neurocognitive disorders.Frontiers in neuroscience · 2025Review
- A Defined Diet Combined with Sonicated Inoculum Provides a High Incidence, Moderate Severity Form of Experimental Autoimmune Encephalomyelitis (EAE).ACS pharmacology & translational science · 2024Article
- Emerging Role of ABC Transporters in Glia Cells in Health and Diseases of the Central Nervous System.Cells · 2024Review
- The Interplay between Ferroptosis and Neuroinflammation in Central Neurological Disorders.Antioxidants (Basel, Switzerland) · 2024Review
- Longitudinal analysis of CSF HIV RNA in untreated people with HIV: Identification of CSF controllers.Journal of medical virology · 2024Article
- Research Progress on the Mechanism of Histone Deacetylases in Ferroptosis of Glioma.Oncology reviews · 2024Review
- CDH4 inhibits ferroptosis in oral squamous cell carcinoma cells.BMC oral health · 2023Article
- New Indole-3-Propionic Acid and 5-Methoxy-Indole Carboxylic Acid Derived Hydrazone Hybrids as Multifunctional Neuroprotectors.Antioxidants (Basel, Switzerland) · 2023Article
- Ferroptosis: a critical player and potential therapeutic target in traumatic brain injury and spinal cord injury.Neural regeneration research · 2023Review
- The Role of Ferroptosis in Blood-Brain Barrier Injury.Cellular and molecular neurobiology · 2023Review
- Review
- Metformin Preserves VE-Cadherin in Choroid Plexus and Attenuates Hydrocephalus via VEGF/VEGFR2/p-Src in an Intraventricular Hemorrhage Rat Model.International journal of molecular sciences · 2022Article
- Synthesis and Optimization of Nitroxide-Based Inhibitors of Ferroptotic Cell Death in Cancer Cells and Macrophages.ACS medicinal chemistry letters · 2022Article
- The Molecular Mechanisms of Ferroptosis and Its Role in Blood-Brain Barrier Dysfunction.Frontiers in cellular neuroscience · 2022Review
- Exosomal delivery of therapeutic modulators through the blood-brain barrier; promise and pitfalls.Cell & bioscience · 2021Review
- A review of studies on vascular dementia and iron metabolism.Science progressReview
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 3 countries.
Funding
Abstract
The objective of this study was to investigate the molecular response to damage at the blood brain barrier (BBB) and to elucidate critical pathways that might lead to effective treatment in central nervous system (CNS) pathologies in which the BBB is compromised. We have used a human, stem-cell derived in-vitro BBB injury model to gain a better understanding of the mechanisms controlling BBB integrity. Chemical injury induced by exposure to an organophosphate resulted in rapid lipid peroxidation, initiating a ferroptosis-like process. Additionally, mitochondrial ROS formation (MRF) and increase in mitochondrial membrane permeability were induced, leading to apoptotic cell death. Yet, these processes did not directly result in damage to barrier functionality, since blocking them did not reverse the increased permeability. We found that the iron chelator, Desferal© significantly decreased MRF and apoptosis subsequent to barrier insult, while also rescuing barrier integrity by inhibiting the labile iron pool increase, inducing HIF2α expression and preventing the degradation of Ve-cadherin specifically on the endothelial cell surface. Moreover, the novel nitroxide JP4-039 significantly rescued both injury-induced endothelium cell toxicity and barrier functionality. Elucidating a regulatory pathway that maintains BBB integrity illuminates a potential therapeutic approach to protect the BBB degradation that is evident in many neurological diseases.
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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.