ArticleScience advances2025
CHI3L1/YKL-40 signaling inhibits neurogenesis in models of Alzheimer's disease.
Article in Science advances, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
11 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Association of Alzheimer's disease progression with YKL40 levels in peripheral blood and cerebrospinal fluid: a systematic review and meta-analysis.Frontiers in neurologyPooled it
- Redefining CHI3L1: Therapeutic Opportunities at the Crossroads of Immune Suppression and Disease Progression.Medicinal research reviews · 2026Review
- Structure-Guided Optimization of CHI3L1 Modulators Reveals G721-0377 as a Lead Compound for Restoring Astrocyte Function in Alzheimer's Disease.ACS bio & med chem Au · 2026Article
- Age-Related Brain Atrophy Mediates a Composite Outcome of One-Year Ischemic Stroke Recurrence and All-Cause Mortality Through YKL-40-Related Inflammatory Pathways: A Structural Equation Model.Translational stroke research · 2026Article
- Relationships of CSF biomarkers to cortical atrophy in early-onset Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Stage-specific CHI3L1/YKL-40 signaling controls generation of oligodendrocyte precursor cells through IL13Rα2-mediated ferroptosis.bioRxiv : the preprint server for biology · 2026Article
- Alzheimer's disease: from molecular pathways to therapies.Molecular biomedicine · 2026Review
- Astrocyte-intrinsic signaling of chitinase-like protein CHI3L1 drives inflammation and amplifies demyelination in neuromyelitis optica.The Journal of clinical investigation · 2026Article
- Elevated CHI3L1 as a Potential Biomarker of Cognitive Dysfunction in Anti-NMDAR Encephalitis: Evidence From Clinical Results and Mice Model.CNS neuroscience & therapeutics · 2026Article
- Review
- ACE2: Friend or Foe in Post-COVID-19 Neurodegeneration?International journal of molecular sciences · 2025Review
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
CHI3L1/YKL-40 is an astrocyte-secreted glycoprotein recognized as a biomarker of CNS inflammation and implicated in Alzheimer's disease (AD) cognitive decline. However, its precise pathological role remains unclear. Here, we investigate CHI3L1's function and its therapeutic potential in AD using both human induced pluripotent stem cell-derived neurogenesis models and in vivo conditional AD mouse models, with astrocyte-specific CHI3L1 knockout, alongside 5XFAD mice. Our data reveal that CHI3L1 secretion by astrocytes impairs neural stem cell (NSC) proliferation and neuronal differentiation by activating the CRTH2 receptor, which triggers a downstream cascade involving IKKβ, S6K1, and S6 phosphorylation. This cascade depletes the NSC pool in the hippocampus, thereby reducing neurogenesis. Notably, targeting astrocytic CHI3L1 or blocking CRTH2 and its downstream effectors substantially restored neurogenesis and cognitive function, highlighting CHI3L1 as a promising therapeutic target for AD and related neurodegenerative disorders.
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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.