ArticleMolecular biology of the cell2007
Gleevec increases levels of the amyloid precursor protein intracellular domain and of the amyloid-beta degrading enzyme neprilysin.
Article in Molecular biology of the cell, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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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
24 citing papers in PubMed, 56 citations in OpenAlex.
- The Hippo signaling pathway as a therapeutic target in Alzheimer's disease.Molecular neurodegeneration · 2025Review
- Abl depletion via autophagy mediates the beneficial effects of quercetin against Alzheimer pathology across species.Cell death discovery · 2023Article
- Therapeutic Targeting of Repurposed Anticancer Drugs in Alzheimer's Disease: Using the Multiomics Approach.ACS omega · 2021Article
- Target Enzymes Considered for the Treatment of Alzheimer's Disease and Parkinson's Disease.BioMed research international · 2020Review
- Quantitative Measurement of γ-Secretase-mediated Amyloid Precursor Protein and Notch Cleavage in Cell-based Luciferase Reporter Assay Platforms.Journal of visualized experiments : JoVE · 2018Article
- ErbB2 regulates autophagic flux to modulate the proteostasis of APP-CTFs in Alzheimer's disease.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Original Research: Featured Article: Imatinib mesylate (Gleevec) inhibits Notch and c-Myc signaling: Five-day treatment permanently rescues mammary development.Experimental biology and medicine (Maywood, N.J.) · 2017Article
- Polyhydroxycurcuminoids but not curcumin upregulate neprilysin and can be applied to the prevention of Alzheimer's disease.Scientific reports · 2016Article
- Nicastrin is required for amyloid precursor protein (APP) but not Notch processing, while anterior pharynx-defective 1 is dispensable for processing of both APP and Notch.Journal of neurochemistry · 2016Article
- New Insights into Epigenetic and Pharmacological Regulation of Amyloid-Degrading Enzymes.Neurochemical research · 2016Article
- Potential role of Notch signalling in CD34+ chronic myeloid leukaemia cells: cross-talk between Notch and BCR-ABL.PloS one · 2015Article
- Hypoxia Affects Neprilysin Expression Through Caspase Activation and an APP Intracellular Domain-dependent Mechanism.Frontiers in neuroscience · 2015Article
- Amyloid-clearing proteins and their epigenetic regulation as a therapeutic target in Alzheimer's disease.Frontiers in aging neuroscience · 2014Review
- Neprilysin and Aβ Clearance: Impact of the APP Intracellular Domain in NEP Regulation and Implications in Alzheimer's Disease.Frontiers in aging neuroscience · 2013Review
- The role of γ-secretase activating protein (GSAP) and imatinib in the regulation of γ-secretase activity and amyloid-β generation.The Journal of biological chemistry · 2013Article
- Association of differential gene expression with imatinib mesylate and omacetaxine mepesuccinate toxicity in lymphoblastoid cell lines.BMC medical genomics · 2012Article
- The amyloid precursor protein has a flexible transmembrane domain and binds cholesterol.Science (New York, N.Y.) · 2012Article
- Mechanisms of Amyloid-β Peptide Clearance: Potential Therapeutic Targets for Alzheimer's Disease.Biomolecules & therapeutics · 2012Review
- The Alzheimer's amyloid-degrading peptidase, neprilysin: can we control it?International journal of Alzheimer's disease · 2012Article
- BRI2 protein regulates β-amyloid degradation by increasing levels of secreted insulin-degrading enzyme (IDE).The Journal of biological chemistry · 2011Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Amyloid-beta (Abeta) deposition is a major pathological hallmark of Alzheimer's disease. Gleevec, a known tyrosine kinase inhibitor, has been shown to lower Abeta secretion, and it is considered a potential basis for novel therapies for Alzheimer's disease. Here, we show that Gleevec decreases Abeta levels without the inhibition of Notch cleavage by a mechanism distinct from gamma-secretase inhibition. Gleevec does not influence gamma-secretase activity in vitro; however, treatment of cell lines leads to a dose-dependent increase in the amyloid precursor protein intracellular domain (AICD), whereas secreted Abeta is decreased. This effect is observed even in presence of a potent gamma-secretase inhibitor, suggesting that Gleevec does not activate AICD generation but instead may slow down AICD turnover. Concomitant with the increase in AICD, Gleevec leads to elevated mRNA and protein levels of the Abeta-degrading enzyme neprilysin, a potential target gene of AICD-regulated transcription. Thus, the Gleevec mediated-increase in neprilysin expression may involve enhanced AICD signaling. The finding that Gleevec elevates neprilysin levels suggests that its Abeta-lowering effect may be caused by increased Abeta-degradation.
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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 Socratic graph.