ArticleProceedings of the National Academy of Sciences of the United States of America2003
Gleevec inhibits beta-amyloid production but not Notch cleavage.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers, 2 of them syntheses that pooled it.
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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.
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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
91 citing papers in PubMed, 2 syntheses or guidelines pooled it, 195 citations in OpenAlex.
- The Role of c-Abl in Alzheimer's Disease: Guilty or not Guilty?Cellular and molecular neurobiology · 2025Pooled it
- Pooled it
- Whole-Genome and Transcriptome Sequencing Identified NOTCH2 and HES1 as Potential Markers of Response to Imatinib in Desmoid Tumor (Aggressive Fibromatosis): A Phase II Trial Study.Cancer research and treatment · 2022Trial
- Quantifying Structural Changes in Cultured Neurons Using Fractal Analysis.Neuroinformatics · 2026Article
- Multi-omics analysis for identifying cell-type-specific and bulk-level druggable targets in Alzheimer's disease.Journal of translational medicine · 2025Article
- The manipulator behind "Scissors": γ -secretase and its modulators in Alzheimer's disease.Frontiers in aging neuroscience · 2025Review
- Revolutionising Neurological Therapeutics: Investigating Drug Repurposing Strategies.CNS & neurological disorders drug targets · 2025Review
- Experimental and clinical tests of FDA-approved kinase inhibitors for the treatment of neurological disorders (update 2024).Exploration of drug science · 2025Article
- Stretching the structural envelope of imatinib to reduce β-amyloid production by modulating both β- and γ-secretase cleavages of APP.Frontiers in chemistry · 2024Article
- Regulation of Peptidase Activity beyond the Active Site in Human Health and Disease.International journal of molecular sciences · 2023Review
- Cancer drugs with high repositioning potential for Alzheimer's disease.Expert opinion on emerging drugs · 2023Review
- An extracellular vesicle targeting ligand that binds to Arc proteins and facilitates Arc transport in vivo.eLife · 2023Article
- FDA-Approved Kinase Inhibitors in Preclinical and Clinical Trials for Neurological Disorders.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Targeting the liver in dementia and cognitive impairment: Dietary macronutrients and diabetic therapeutics.Advanced drug delivery reviews · 2022Review
- γ-Secretase in Alzheimer's disease.Experimental & molecular medicine · 2022Review
- CCR5 antagonist reduces HIV-induced amyloidogenesis, tau pathology, neurodegeneration, and blood-brain barrier alterations in HIV-infected hu-PBL-NSG mice.Molecular neurodegeneration · 2021Article
- Probing Mechanisms and Therapeutic Potential of γ-Secretase in Alzheimer's Disease.Molecules (Basel, Switzerland) · 2021Review
- Brain Permeable Tafamidis Amide Analogs for Stabilizing TTR and Reducing APP Cleavage.ACS medicinal chemistry letters · 2020Article
- A Pentacyclic Triterpene fromACS chemical neuroscience · 2020Article
- Marine Natural Products, Multitarget Therapy and Repurposed Agents in Alzheimer's Disease.Pharmaceuticals (Basel, Switzerland) · 2020Review
31 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Amyloid-beta (Abeta) peptides, consisting mainly of 40 and 42 aa (Abeta40 and Abeta42, respectively), are metabolites of the amyloid precursor protein and are believed to be major pathological determinants of Alzheimer's disease. The proteolytic cleavages that form the Abeta N and C termini are catalyzed by beta-secretase and gamma-secretase, respectively. Here we demonstrate that gamma-secretase generation of Abeta in an N2a cell-free system is ATP dependent. In addition, the Abl kinase inhibitor imatinib mesylate (Gleevec, or STI571), which targets the ATP-binding site of Abl and several other tyrosine kinases, potently reduces Abeta production in the N2a cell-free system and in intact N2a cells. Both STI571 and a related compound, inhibitor 2, also reduce Abeta production in rat primary neuronal cultures and in vivo in guinea pig brain. STI571 does not inhibit the gamma-secretase-catalyzed S3 cleavage of Notch-1. Furthermore, production of Abeta and its inhibition by STI571 were demonstrated to occur to similar extents in both Abl-/- and WT mouse fibroblasts, indicating that the effect of STI571 on Abeta production does not involve Abl kinase. The efficacy of STI571 in reducing Abeta without affecting Notch-1 cleavage may prove useful as a basis for developing novel therapies for Alzheimer's disease.
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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.