ArticleMolecular neurodegeneration2023
The Alzheimer's disease-linked protease BACE1 modulates neuronal IL-6 signaling through shedding of the receptor gp130.
Article in Molecular neurodegeneration, 2023. 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, 41 citations in OpenAlex.
- Association of MOCA Cognitive Domains and Serum Biomarkers With Anxiety Disorders in Elderly Men With Cognitive Impairment: A Cross-Sectional Analysis.Revista de neurologia · 2026Article
- Decoding unchanged transcriptome of Alzheimer's disease reveals an NCAM1 mRNA switch as a potential biomarker.iScience · 2026Article
- BACE1 regulates sleep-wake cycle through both enzymatic and non-enzymatic actions.EMBO reports · 2026Article
- Elenbecestat and Compound 89 Potently Inhibit BACE1 but Not BACE2 When Subchronically Dosed in Non-Human Primates.Proteomics · 2026Article
- ZuoGui Pill Ameliorates Alzheimer's Disease-Like Pathology in 3xTg-AD Mice by Targeting Aβ Production, Tau Phosphorylation, Synaptic Loss, and Neuroinflammation.Molecular neurobiology · 2025Article
- The Ubiquitin-Proteasome System in Brain Disorders: Pathogenic Pathways, Post-Translational Tweaks, and Therapeutic Frontiers.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2025Review
- Type I interferon limits interleukin-6 signalling in SLE through shedding interleukin-6 receptors.Rheumatology (Oxford, England) · 2025Article
- MolCL-SP: a multimodal contrastive learning framework with non-overlapping substructure perturbations for molecular property prediction.Bioinformatics (Oxford, England) · 2025Article
- Discovery of an APP-selective BACE1 inhibitor for Alzheimer's disease.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Article
- Gnb5 is a negative regulator of the BACE1-mediated Aβ generation and ameliorates cognitive deficits in a mouse model of Alzheimer's disease.PLoS biology · 2025Article
- IL-6 Signaling in Immunopathology: From Basic Biology to Selective Therapeutic Intervention.ImmunoTargets and therapy · 2025Review
- Contribution of amyloid deposition from oligodendrocytes in a mouse model of Alzheimer's disease.Molecular neurodegeneration · 2024Article
- Exploring the role of interleukin-6 receptor blockade in epilepsy and associated neuropsychiatric conditions through a mendelian randomization study.World journal of psychiatry · 2024Article
- Multicolor, Cell-Impermeable, and High Affinity BACE1 Inhibitor Probes Enable Superior Endogenous Staining and Imaging of Single Molecules.Journal of medicinal chemistry · 2024Article
- The Alzheimer's disease-linked protease BACE2 cleaves VEGFR3 and modulates its signaling.The Journal of clinical investigation · 2024Article
- Associations of CSF BACE1 with amyloid pathology, neurodegeneration, and cognition in Alzheimer's disease.Acta neuropathologica · 2024Article
- Roles of Cytokines in Alzheimer's Disease.International journal of molecular sciences · 2024Review
- Alzheimer's disease and its treatment-yesterday, today, and tomorrow.Frontiers in pharmacology · 2024Review
- Long-term increase in soluble interleukin-6 receptor levels in convalescents after mild COVID-19 infection.Frontiers in immunology · 2024Article
- Advancements and Challenges in Antiamyloid Therapy for Alzheimer's Disease: A Comprehensive Review.International journal of Alzheimer's disease · 2024Review
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe protease BACE1 is a major drug target for Alzheimer's disease, but chronic BACE1 inhibition is associated with non-progressive cognitive worsening that may be caused by modulation of unknown physiological BACE1 substrates.
methodsTo identify in vivo-relevant BACE1 substrates, we applied pharmacoproteomics to non-human-primate cerebrospinal fluid (CSF) after acute treatment with BACE inhibitors.
resultsBesides SEZ6, the strongest, dose-dependent reduction was observed for the pro-inflammatory cytokine receptor gp130/IL6ST, which we establish as an in vivo BACE1 substrate. Gp130 was also reduced in human CSF from a clinical trial with a BACE inhibitor and in plasma of BACE1-deficient mice. Mechanistically, we demonstrate that BACE1 directly cleaves gp130, thereby attenuating membrane-bound gp130 and increasing soluble gp130 abundance and controlling gp130 function in neuronal IL-6 signaling and neuronal survival upon growth-factor withdrawal.
conclusionBACE1 is a new modulator of gp130 function. The BACE1-cleaved, soluble gp130 may serve as a pharmacodynamic BACE1 activity marker to reduce the occurrence of side effects of chronic BACE1 inhibition in humans.
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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.