ArticleInternational journal of molecular sciences2021
Donepezil Regulates LPS and Aβ-Stimulated Neuroinflammation through MAPK/NLRP3 Inflammasome/STAT3 Signaling.
Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers, 2 of them syntheses that pooled it.
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Who cites it
79 citing papers in PubMed, 2 syntheses or guidelines pooled it, 137 citations in OpenAlex.
- Pooled it
- Efficacy of acetylcholinesterase inhibitors on reducing hippocampal atrophy rate: a systematic review and meta-analysis.BMC neurology · 2025Pooled it
- AMBMP Hydrochloride Reverses STZ-Induced Alzheimer-Type Dementia Associated with Wnt/β-catenin/TLR4 Signaling.Neuromolecular medicine · 2026Article
- Targeting the Redox-NF-κB/NLRP3 axis with intranasal liposomal minocycline mitigates aluminum-induced cognitive and structural deficits.Molecular biology reports · 2026Article
- Maltol Protects Neuronal Cells by Alleviating Chronic Neuroinflammation, Pyroptosis, and Ferroptosis via HSP70 Upregulation in Microglia.Nutrients · 2026Article
- The effect of canagliflozin on hippocampal dendrite morphology in a model of Alzheimer's disease induced by intracerebroventricular injection of streptozotocin.Brain structure & function · 2026Article
- Article
- The insulin receptor inhibitor BMS-754807 alleviates neuroinflammation and Alzheimer's disease pathologies across human cellular and mouse models.Journal of neuroinflammation · 2026Article
- Glibenclamide attenuates osteoarthritis by suppressing NLRP3 inflammasome activation in synovial macrophages through the MAPK pathway.Journal of translational medicine · 2026Article
- Exploring the toxic mechanism of cypermethrin-induced neurodegeneration diseases via network toxicology and molecular docking.Scientific reports · 2026Article
- Neuro-Immune Crosstalk: Molecular Mechanisms, Biological Functions, Diseases, and Therapeutic Targets.MedComm · 2026Review
- [Sulforaphane reduces reactive astrocyte-mediated neuron apoptosisNan fang yi ke da xue xue bao = Journal of Southern Medical University · 2026Article
- Unveiling the neuroprotective effects of pomegranate extract and/or physical activity against aluminum chloride-induced Alzheimer's disease in rats: modulation of multitude pathways.Frontiers in pharmacology · 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
- A new mechanism regulating microglial NLRP3 inflammasome: FMR1 mediates NLRP3 mRNA stability.PloS one · 2026Article
- Neuroinflammation demonstrated byAlzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Dietary dihydroquercetin alleviates age-related cognitive impairment in association with modulation of apoptosis and pyroptosis pathways.Frontiers in pharmacology · 2026Article
- Luteolin in Safflower Leaves Suppresses Microglial Inflammation Through FOXO3-MediatedAntioxidants (Basel, Switzerland) · 2025Article
- Geniposide attenuates astrocyte pyroptosis in depression via long non-coding RNA Six3os1-mediated regulation of the miR-511-3p/COL9A3 axis and MAPK/NLRP3 signaling.Journal of cell communication and signaling · 2025Article
- Multiple Mechanisms and Therapeutic Strategies for the Involvement of AMPK in the Development of Alzheimer's Disease.Molecular neurobiology · 2025Review
19 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
The acetylcholinesterase inhibitors donepezil and rivastigmine have been used as therapeutic drugs for Alzheimer's disease (AD), but their effects on LPS- and Aβ-induced neuroinflammatory responses and the underlying molecular pathways have not been studied in detail in vitro and in vivo. In the present study, we found that 10 or 50 μM donepezil significantly decreased the LPS-induced increases in the mRNA levels of a number of proinflammatory cytokines in BV2 microglial cells, whereas 50 μM rivastigmine significantly diminished only LPS-stimulated IL-6 mRNA levels. In subsequent experiments in primary astrocytes, donepezil suppressed only LPS-stimulated iNOS mRNA levels. To identify the molecular mechanisms by which donepezil regulates LPS-induced neuroinflammation, we examined whether donepezil alters LPS-stimulated proinflammatory responses by modulating LPS-induced downstream signaling and the NLRP3 inflammasome. Importantly, we found that donepezil suppressed LPS-induced AKT/MAPK signaling, the NLRP3 inflammasome, and transcription factor NF-kB/STAT3 phosphorylation to reduce neuroinflammatory responses. In LPS-treated wild-type mice, a model of neuroinflammatory disease, donepezil significantly attenuated LPS-induced microglial activation, microglial density/morphology, and proinflammatory cytokine COX-2 and IL-6 levels. In a mouse model of AD (5xFAD mice), donepezil significantly reduced Aβ-induced microglial and astrocytic activation, density, and morphology. Taken together, our findings indicate that donepezil significantly downregulates LPS- and Aβ-evoked neuroinflammatory responses in vitro and in vivo and may be a therapeutic agent for neuroinflammation-associated diseases such as AD.
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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.