ArticleFrontiers in aging neuroscience2015
Intranasal deferoxamine attenuates synapse loss via up-regulating the P38/HIF-1α pathway on the brain of APP/PS1 transgenic mice.
Article in Frontiers in aging neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 75 citations in OpenAlex.
- Cell Death in Neurodegenerative Diseases: Molecular Mechanisms and Therapeutic Targets.MedComm · 2026Review
- The Role of Cytochrome P450 Holoenzyme Metabolism in the Origin of Neuropathologies.International journal of molecular sciences · 2026Review
- Targeting Hippocampal PTEN Suppresses Ferroptosis and Rescues Cognitive Decline in Alzheimer's Disease via Dual AKT/GSK3β/Nrf2 and AKT/STAT3 Axes.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Hypoxia inducible factor-1α-driven signaling networks regulating adult neurogenesis via Notch, Wnt, and MAPK pathways.Molecular biology reports · 2026Review
- Cell type-specific gene regulatory atlas prioritizes drug targets and repurposable medicines in Alzheimer's disease.Genome research · 2026Article
- Inherently bioactive iron-chelating Poly (N-acryloyl 2-glycine)/chitosan hydrogel scaffolds orchestrating dual hypoxic-immune microenvironment for functional meniscus regeneration.Bioactive materials · 2025Article
- Hypoxic Natural Killer Cells-Derived HIF-1α-Containing Exosomes Inhibit Cellular Senescence and Apoptosis in Neurocytes to Ameliorate Alzheimer's Disease by Eliminating Oxidative Damages.Molecular neurobiology · 2025Article
- Targeting hypoxia-related pathobiology in Alzheimer's disease: strategies for prevention and treatment.Molecular biology reports · 2025Review
- Homeostasis and metabolism of iron and other metal ions in neurodegenerative diseases.Signal transduction and targeted therapy · 2025Review
- The role of protein phosphorylation modifications mediated by iron metabolism regulatory networks in the pathogenesis of Alzheimer's disease.Frontiers in aging neuroscience · 2025Review
- Intranasal delivery of iron chelators and management of central nervous system disease.Frontiers in pharmacology · 2025Review
- The impact of high-intensity interval training on cerebrovascular function in the APP/PS1 mice.Frontiers in aging · 2025Article
- Potential Roles of Hypoxia-Inducible Factor-1 in Alzheimer's Disease: Beneficial or Detrimental?Antioxidants (Basel, Switzerland) · 2024Review
- Increased Expression of Transferrin Receptor 1 in the Brain Cortex of 5xFAD Mouse Model of Alzheimer's Disease Is Associated with Activation of HIF-1 Signaling Pathway.Molecular neurobiology · 2024Article
- Targeting Biometals in Alzheimer's Disease with Metal Chelating Agents Including Coumarin Derivatives.CNS drugs · 2024Review
- Iron and Targeted Iron Therapy in Alzheimer's Disease.International journal of molecular sciences · 2023Review
- Iron Chelator Deferoxamine Alleviates Progression of Diabetic Nephropathy by Relieving Inflammation and Fibrosis in Rats.Biomolecules · 2023Article
- Host cell egress of Brucella abortus requires BNIP3L-mediated mitophagy.The EMBO journal · 2023Article
- Brain Iron Metabolism, Redox Balance and Neurological Diseases.Antioxidants (Basel, Switzerland) · 2023Review
- Challenges and Opportunities of Metal Chelation Therapy in Trace Metals Overload-Induced Alzheimer's Disease.Neurotoxicity research · 2023Review
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8 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
The widely recognized neuroprotective effect of iron chelators is contributed by their ability to prevent reactive oxygen species (ROS) generation via the Fenton reaction, which sequesters redox-active Fe. An additional neuroprotective mechanism of iron-chelating compounds is to regulate the transcriptional activator hypoxia-inducible factor 1α (HIF-1α). In the present study, we observed that intranasal administration of deferoxamine decreased beta-amyloid (Aβ) deposition and rescued synapse loss in the brain of Aβ precursor protein and presenilin-1 (APP/PS1) double transgenic mice. We found that deferoxamine (DFO) up-regulated HIF-1α mRNA expression and its protein level, and further induced the proteins that are encoded from HIF-1-adaptive genes, including transferrin receptor (TFR), divalent metal transporter 1 (DMT1), and brain-derived neurotrophic factor (BDNF). The effects of DFO on the induction and stabilization of HIF-1α were further confirmed in vitro. This was accompanied by a decrease of Fe in the CA3 region of the hippocampus. Western blotting studies revealed that DFO differentially enhanced the phosphorylation of mitogen-activated protein kinase (MAPK)/P38 kinase in vitro and in vivo. The results suggest that the DFO may up-regulate several HIF-1-dependent neuroprotective-adaptive genes in AD via activating P38/HIF-1α pathway, which may serve as important therapeutic targets to the disease.
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