ArticleNature communications2017
Inhibition of delta-secretase improves cognitive functions in mouse models of Alzheimer's disease.
Article in Nature communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers.
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.
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Who cites it
83 citing papers in PubMed, 141 citations in OpenAlex.
- Endothelial C/EBPβ/AEP pathway drives vascular deterioration and systemic aging.Science advances · 2026Article
- Protease-Mediated TAR DNA-Binding Protein 43 (TDP-43) Pathogenesis: From Molecular Mechanisms to Therapeutic Opportunities.ACS pharmacology & translational science · 2026Review
- Advances in Alzheimer's disease: mechanistic insights and therapeutic targets.Science China. Life sciences · 2026Review
- Distinct factors drive the progression of tau pathology in Alzheimer's disease.Fundamental research · 2026Review
- Positional scanning and computational modeling reveal determinants of legumain transpeptidase activity.Protein science : a publication of the Protein Society · 2026Article
- Alzheimer's Disease: From Pathogenesis to Emerging Therapeutic Targets.Journal of clinical medicine · 2026Review
- Monocyte-Derived LGMNResearch (Washington, D.C.) · 2026Article
- Asparagine endopeptidase (AEP) inhibitor formulation via zein-based nanoparticle improves the therapeutic efficacy toward Alzheimer's disease.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Article
- Employing complementary fractionation-based N-terminomics approaches enhances the identification of legumain cleavage events in naïve and inflamed colon tissue.Protein science : a publication of the Protein Society · 2025Article
- Asparagine endopeptidase cleaves apolipoprotein A1 and accelerates pathogenesis of atherosclerosis.The Journal of clinical investigation · 2025Article
- Targeting legumain-mediated cell-cell interaction sensitizes glioblastoma to immunotherapy in preclinical models.The Journal of clinical investigation · 2025Article
- Intraneuronal Aβ accumulation causes tau hyperphosphorylation via endolysosomal leakage.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Microglia Process α-Synuclein Fibrils and Enhance their Pathogenicity in a TREM2-Dependent Manner.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Roles of C/EBPβ/AEP in Neurodegenerative Diseases.Current topics in medicinal chemistry · 2025Review
- Sox6 and ALDH1A1 Truncation by Asparagine Endopeptidase Defines Selective Neuronal Vulnerability in Parkinson's Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Updates in Alzheimer's disease: from basic research to diagnosis and therapies.Translational neurodegeneration · 2024Review
- Tau in neurodegenerative diseases: molecular mechanisms, biomarkers, and therapeutic strategies.Translational neurodegeneration · 2024Review
- Heat-related illness and dementia: a study integrating epidemiological and experimental evidence.Alzheimer's research & therapy · 2024Article
- STAT3 ameliorates truncated tau-induced cognitive deficits.Neural regeneration research · 2024Article
- Inhibition of asparagine endopeptidase (AEP) effectively treats sporadic Alzheimer's disease in mice.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Article
23 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 3 countries.
Funding
Abstract
δ-secretase, also known as asparagine endopeptidase (AEP) or legumain, is a lysosomal cysteine protease that cleaves both amyloid precursor protein (APP) and tau, mediating the amyloid-β and tau pathology in Alzheimer's disease (AD). Here we report the therapeutic effect of an orally bioactive and brain permeable δ-secretase inhibitor in mouse models of AD. We performed a high-throughput screen and identified a non-toxic and selective δ-secretase inhibitor, termed compound 11, that specifically blocks δ-secretase but not other related cysteine proteases. Co-crystal structure analysis revealed a dual active site-directed and allosteric inhibition mode of this compound class. Chronic treatment of tau P301S and 5XFAD transgenic mice with this inhibitor reduces tau and APP cleavage, ameliorates synapse loss and augments long-term potentiation, resulting in protection of memory. Therefore, these findings demonstrate that this δ-secretase inhibitor may be an effective clinical therapeutic agent towards 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.