ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2024
Neurotoxic Microglial Activation via IFNγ-Induced Nrf2 Reduction Exacerbating Alzheimer's Disease.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 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
23 citing papers in PubMed, 18 citations in OpenAlex.
- MAFG as a Redox-Sensitive Node Linking Peripheral Immune Reprogramming to Cognitive Risk in the Sepsis-to-Alzheimer's Disease Continuum: Single-Cell Dissection and Adoptive-Transfer Validation.CNS neuroscience & therapeutics · 2026Article
- Molecular Editing Reveals a Bilobalide Chemotype that Attenuates Prolyl Endopeptidase (PREP)-Linked Neuroinflammation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- N 6 -methyladenosine modification regulates cell death in cognitive impairment.Neural regeneration research · 2026Article
- Microglia and neuroinflammation: function, heterogeneity, and crosstalk.Cellular & molecular immunology · 2026Review
- Microglia maintain retinal redox homeostasis following ablation of rod photoreceptors in zebrafish.The Journal of biological chemistry · 2026Article
- Microglia Attenuate Neuroinflammation After Subarachnoid Hemorrhage by Modulating Astrocyte Phenotypic Transformation via the RARα/Mafb/Msr1 Pathway.Molecular neurobiology · 2026Article
- Neuroinflammation and Secretase Regulation in Alzheimer's Disease: From Molecular Cross-Talk to Multi-Target Therapeutics.International journal of molecular sciences · 2026Review
- Targeting the Gut-Brain Axis: Protective Effects of NMN in Alleviating D-Galactose-Induced Cognitive Deficits.Metabolites · 2026Article
- Advances in hiPSC-Derived Brain Organoids as a Model to Study Neuroinflammation in Alzheimer's Disease.Journal of neurochemistry · 2026Review
- Bioreactor expansion of human neural progenitor cells for exosome scalable production and miRNA-engineering.Journal of biological engineering · 2026Article
- Targeting glial cells: Unveiling the neuroprotective mechanisms of Ginseng in the brain microenvironment.Acta pharmaceutica Sinica. B · 2026Review
- Modeling Alzheimer's disease with brain organoids: mechanisms, applications, and future directions.Frontiers in cell and developmental biology · 2026Review
- A study to determine the effect of nano-selenium and thymoquinone on the Nrf2 gene expression in Alzheimer's disease.Future science OA · 2025Article
- The Redox Revolution in Brain Medicine: Targeting Oxidative Stress with AI, Multi-Omics and Mitochondrial Therapies for the Precision Eradication of Neurodegeneration.International journal of molecular sciences · 2025Review
- Modulatory Effects ofAntioxidants (Basel, Switzerland) · 2025Review
- Mitochondrial quality control disorder in neurodegenerative disorders: Potential and advantages of traditional Chinese medicines.Journal of pharmaceutical analysis · 2025Review
- Berberine-loaded iron oxide nanoparticles alleviate cuprizone-induced astrocytic reactivity in a rat model of multiple sclerosis.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2025Article
- Review
- Novel floxed cannabinoid receptor 2 mouse line combines knockout capability with dual fluorescent reporters.Frontiers in pharmacology · 2025Article
- Mapping microglial mechanisms in Alzheimer's disease: a comprehensive analysis.Experimental biology and medicine (Maywood, N.J.) · 2025Article
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 2 countries.
Funding
Abstract
Microglial neuroinflammation appears to be neuroprotective in the early pathological stage, yet neurotoxic, which often precedes neurodegeneration in Alzheimer's disease (AD). However, it remains unclear how the microglial activities transit to the neurotoxic state during AD progression, due to complex neuron-glia interactions. Here, the mechanism of detrimental microgliosis in AD by employing 3D human AD mini-brains, brain tissues of AD patients, and 5XFAD mice is explored. In the human and animal AD models, amyloid-beta (Aβ)-overexpressing neurons and reactive astrocytes produce interferon-gamma (IFNγ) and excessive oxidative stress. IFNγ results in the downregulation of mitogen-activated protein kinase (MAPK) and the upregulation of Kelch-like ECH-associated Protein 1 (Keap1) in microglia, which inactivate nuclear factor erythroid-2-related factor 2 (Nrf2) and sensitize microglia to the oxidative stress and induces a proinflammatory microglia via nuclear factor kappa B (NFκB)-axis. The proinflammatory microglia in turn produce neurotoxic nitric oxide and proinflammatory mediators exacerbating synaptic impairment, phosphorylated-tau accumulation, and discernable neuronal loss. Interestingly, recovering Nrf2 in the microglia prevents the activation of proinflammatory microglia and significantly blocks the tauopathy in AD minibrains. Taken together, it is envisioned that IFNγ-driven Nrf2 downregulation in microglia as a key target to ameliorate AD pathology.
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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.