ArticleJournal of neuroinflammation2020
K284-6111 alleviates memory impairment and neuroinflammation in Tg2576 mice by inhibition of Chitinase-3-like 1 regulating ERK-dependent PTX3 pathway.
Article in Journal of neuroinflammation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 42 citations in OpenAlex.
- Structural optimization of CHI3L1 inhibitors with improved pharmacokinetics and functional activity in 3D glioblastoma models.Journal of enzyme inhibition and medicinal chemistry · 2026Article
- Redefining CHI3L1: Therapeutic Opportunities at the Crossroads of Immune Suppression and Disease Progression.Medicinal research reviews · 2026Review
- Review
- The emerging role of astrocytes in spatial cognition, action and Alzheimer's disease.Frontiers in cellular neuroscience · 2026Review
- CHI3L1: An Emerging Player in Neuroinflammation and Neurodegeneration.Molecular neurobiology · 2025Review
- CHI3L1-targeted small molecules as glioblastoma therapies: Virtual screening-based discovery, biophysical validation, pharmacokinetic profiling, and evaluation in glioblastoma spheroids.European journal of medicinal chemistry · 2025Article
- Plasma CHI3L1 associates with brain volume loss and glial activation in multiple sclerosis.Journal of neurology, neurosurgery, and psychiatry · 2025Article
- Chitinase-3-Like Protein 1 as a Therapeutic Target for Inflammatory Diseases.Biomolecules & therapeutics · 2025Review
- From Amyloid to Synaptic Dysfunction: Biomarker-Driven Insights into Alzheimer's Disease.Current issues in molecular biology · 2025Review
- Magnolol Ameliorates Depression Through Modulating the TREM2-DOK3-ERK Pathway.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2025Article
- Inhibition of CHI3L1 attenuates excessive autophagy in intestinal epithelial cells to reduce the severity of necrotizing enterocolitis.Cell death discovery · 2025Article
- Anti-arthritis Effect of Anti-chitinase-3-like 1 Antibody Through Inhibition of MMP3.Immune network · 2025Article
- Chitinase-3-like-1: a multifaceted player in neuroinflammation and degenerative pathologies with therapeutic implications.Molecular neurodegeneration · 2025Review
- CHI3L1 monoclonal antibody therapy mitigates cognitive impairment by inhibiting neuroinflammation through ERK and NF-κB pathway in Tg2576 mice.Frontiers in molecular neuroscience · 2025Article
- Advances in understanding the role of pentraxin-3 in lung infections.Frontiers in immunology · 2025Review
- Inflammatory Effects and Regulatory Mechanisms of Chitinase-3-like-1 in Multiple Human Body Systems: A Comprehensive Review.International journal of molecular sciences · 2024Review
- Inhibition of Amyloid-β (Aβ)-Induced Cognitive Impairment and Neuroinflammation in CHI3L1 Knockout Mice through Downregulation of ERK-PTX3 Pathway.International journal of molecular sciences · 2024Article
- Astrocyte-specific knockout of YKL-40/Chi3l1 reduces Aβ burden and restores memory functions in 5xFAD mice.Journal of neuroinflammation · 2023Article
- Potential Roles and Future Perspectives of Chitinase 3-like 1 in Macrophage Polarization and the Development of Diseases.International journal of molecular sciences · 2023Review
- Inflammatory signaling pathways in the treatment of Alzheimer's disease with inhibitors, natural products and metabolites (Review).International journal of molecular medicine · 2023Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
backgroundAlzheimer's disease (AD) is one of the most prevalent neurodegenerative disorders characterized by gradual memory loss and neuropsychiatric symptoms. We have previously demonstrated that the 2-({3-[2-(1-cyclohexene-1-yl)ethyl]-6,7-dimethoxy-4-oxo-3,4-dihydro-2-quinazolinyl}sulfanyl)-N-(4-ethylphenyl)butanamide (K284-6111), the inhibitor of CHI3L1, has the inhibitory effect on memory impairment in Αβ infusion mouse model and on LPS-induced neuroinflammation in the murine BV-2 microglia and primary cultured astrocyte.
methodsIn the present study, we investigated the inhibitory effect of K284-6111 on memory dysfunction and neuroinflammation in Tg2576 transgenic mice, and a more detailed correlation of CHI3L1 and AD. To investigate the effects of K284-6111 on memory dysfunction, we administered K284-6111 (3 mg/kg, p.o.) daily for 4 weeks to Tg2576 mice, followed by behavioral tests of water maze test, probe test, and passive avoidance test.
resultsAdministration of K284-6111 alleviated memory impairment in Tg2576 mice and had the effect of reducing the accumulation of Aβ and neuroinflammatory responses in the mouse brain. K284-6111 treatment also selectively inactivated ERK and NF-κB pathways, which were activated when CHI3L1 was overexpressed, in the mouse brain and in BV-2 cells. Web-based gene network analysis and our results of gene expression level in BV-2 cells showed that CHI3L1 is closely correlated with PTX3. Our result revealed that knockdown of PTX3 has an inhibitory effect on the production of inflammatory proteins and cytokines, and on the phosphorylation of ERK and IκBα.
conclusionThese results suggest that K284-6111 could improve memory dysfunction by alleviating neuroinflammation through inhibiting CHI3L1 enhancing ERK-dependent PTX3 pathway.
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Registered trials
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