ArticleMolecular neurobiology2022
Hippocampal Iron Accumulation Impairs Synapses and Memory via Suppressing Furin Expression and Downregulating BDNF Maturation.
Article in Molecular neurobiology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 26 citations in OpenAlex.
- The Role of Brain-Derived Neurotrophic Factor (BDNF) in Neural Development and Cognitive Behavior in Pigeons: Advances and Future Perspectives.Current issues in molecular biology · 2026Review
- Proteomics signatures associated with cognitive trajectories: evidence from the English Longitudinal Study of Ageing.medRxiv : the preprint server for health sciences · 2026Article
- Pseudohypoxia induced by iron chelators preserves working memory performance in aged mice.Scientific reports · 2026Article
- 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
- The Potential Regulators of Amyloidogenic Pathway of APP Processing in Alzheimer's Disease.Biomedicines · 2025Review
- Ferroptosis as a potential molecular mechanism of bipolar disorder.Translational psychiatry · 2025Review
- Plasma proteomic biomarkers and the association between poor cardiovascular health and incident dementia: The UK Biobank study.Brain, behavior, and immunity · 2024Article
- Advancements in understanding the role of ferroptosis in hypoxia-associated brain injury: a narrative review.Translational pediatrics · 2024Review
- Obstructive sleep apnea affects cognition: dual effects of intermittent hypoxia on neurons.Sleep & breathing = Schlaf & Atmung · 2024Review
- Iron Overload in Brain: Transport Mismatches, Microbleeding Events, and How Nanochelating Therapies May Counteract Their Effects.International journal of molecular sciences · 2024Review
- Cellular iron depletion enhances behavioral rhythm by limiting brain Per1 expression in mice.CNS neuroscience & therapeutics · 2024Article
- Hepcidin deficiency impairs hippocampal neurogenesis and mediates brain atrophy and memory decline in mice.Journal of neuroinflammation · 2024Article
- Amyloid Precursor Protein and Alzheimer's Disease.International journal of molecular sciences · 2023Review
- Brain Iron Metabolism, Redox Balance and Neurological Diseases.Antioxidants (Basel, Switzerland) · 2023Review
- Non-Enzymatic Antioxidants against Alzheimer's Disease: Prevention, Diagnosis and Therapy.Antioxidants (Basel, Switzerland) · 2023Review
- Huperzine A-Liposomes Efficiently Improve Neural Injury in the Hippocampus of Mice with Chronic Intermittent Hypoxia.International journal of nanomedicine · 2023Article
- The emerging role of furin in neurodegenerative and neuropsychiatric diseases.Translational neurodegeneration · 2022Review
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Brain iron overload is positively correlated with the pathogenesis of Alzheimer's disease (AD). However, the role of iron in AD pathology is not completely understood. Furin is the first identified mammalian proprotein convertase that catalyzes the proteolytic maturation of large numbers of prohormones and proproteins. The correlation between altered furin expression and AD pathology has been suggested, but the underlying mechanism remains to be clarified. Here, we found that the expression of furin in the hippocampus of Alzheimer's model APP/PS1 mice was significantly reduced, and we demonstrated that the reduction of furin was directly caused by hippocampal iron overload using wild-type mice with intrahippocampal injection of iron. In cultured neuronal cells, this suppression effect was observed as transcriptional inhibition. Regarding the changes of furin-mediated activities caused by hippocampal iron overload, we found that the maturation of brain-derived neurotrophic factor (BDNF) was impeded and the expression levels of synaptogenesis-related proteins were downregulated, leading to cognitive decline. Furthermore, iron chelation or furin overexpression in the hippocampus of APP/PS1 mice increased furin expression, restored synapse plasticity, and ameliorated cognitive decline. Therefore, the inhibitory effect of hippocampal iron accumulation on furin transcription may be an important pathway involved in iron-mediated synapse damage and memory loss in AD. This study provides new insights into the molecular mechanisms of the toxic effects of iron in neurons and AD pathophysiology and renders furin as a potential target for treatment of iron overload-related neurodegenerative 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 Socratic graph.