ArticleThe Journal of biological chemistry2013
The role of γ-secretase activating protein (GSAP) and imatinib in the regulation of γ-secretase activity and amyloid-β generation.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 47 citations in OpenAlex.
- Comparative Evaluation of Imatinib and Nilotinib in a Streptozotocin-Induced Rat Model of Alzheimer's Disease : Neuroprotective, Anti-inflammatory, and Cognitive Outcomes.Journal of Korean Neurosurgical Society · 2026Article
- Prioritizing repurposable drugs for Alzheimer's disease using network-based analysis with concurrent assessment of Long QT syndrome risk.Biotechnology reports (Amsterdam, Netherlands) · 2025Article
- Experimental and clinical tests of FDA-approved kinase inhibitors for the treatment of neurological disorders (update 2024).Exploration of drug science · 2025Article
- Proposed Therapeutic Strategy to Combat Alzheimer's Disease by Targeting Beta and Gamma Secretases.Current Alzheimer research · 2025Review
- Neprilysin-Mediated Amyloid Beta Clearance and Its Therapeutic Implications in Neurodegenerative Disorders.ACS pharmacology & translational science · 2024Review
- Gamma secretase activating protein promotes end-organ dysfunction after bacterial pneumonia.American journal of physiology. Lung cellular and molecular physiology · 2023Article
- To Explore the Binding Affinity of Human γ-Secretase Activating Protein (GSAP) Isoform 4 with APP-C99 Peptides.ACS omega · 2023Article
- FDA-Approved Kinase Inhibitors in Preclinical and Clinical Trials for Neurological Disorders.Pharmaceuticals (Basel, Switzerland) · 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
- Chemotherapy and the Risk of Alzheimer's Disease in Colorectal Cancer Survivors: Evidence From the Medicare System.JCO oncology practice · 2021Article
- Associations of circulating mediators of inflammation, cell regulation and immune response with esophageal squamous cell carcinoma.Journal of cancer research and clinical oncology · 2021Article
- Protective Role of a Donepezil-Huprine Hybrid against the β-Amyloid (1-42) Effect on Human Erythrocytes.International journal of molecular sciences · 2021Article
- GSAP regulates lipid homeostasis and mitochondrial function associated with Alzheimer's disease.The Journal of experimental medicine · 2021Article
- γ-Secretase inhibitors and modulators: Mechanistic insights into the function and regulation of γ-Secretase.Seminars in cell & developmental biology · 2020Review
- Genome-wide identification of methylated CpG sites in nongenital cutaneous warts.BMC medical genomics · 2020Article
- Molecular Pathogenesis and Interventional Strategies for Alzheimer's Disease: Promises and Pitfalls.ACS pharmacology & translational science · 2020Review
- Beta-Amyloid-Dependent miRNAs as Circulating Biomarkers in Alzheimer's Disease: a Preliminary Report.Journal of molecular neuroscience : MN · 2020Article
- γ-Secretase Modulatory Proteins: The Guiding Hand Behind the Running Scissors.Frontiers in aging neuroscience · 2020Article
- GSAP modulates γ-secretase specificity by inducing conformational change in PS1.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
γ-Secretase is a large enzyme complex comprising presenilin, nicastrin, presenilin enhancer 2, and anterior pharynx-defective 1 that mediates the intramembrane proteolysis of a large number of proteins including amyloid precursor protein and Notch. Recently, a novel γ-secretase activating protein (GSAP) was identified that interacts with γ-secretase and the C-terminal fragment of amyloid precursor protein to selectively increase amyloid-β production. In this study we have further characterized the role of endogenous and exogenous GSAP in the regulation of γ-secretase activity and amyloid-β production in vitro. Knockdown of GSAP expression in N2a cells decreased amyloid-β levels. In contrast, overexpression of GSAP in HEK cells expressing amyloid precursor protein or in N2a cells had no overt effect on amyloid-β generation. Likewise, purified recombinant GSAP had no effect on amyloid-β generation in two distinct in vitro γ-secretase assays. In subsequent cellular studies with imatinib, a kinase inhibitor that reportedly prevents the interaction of GSAP with the C-terminal fragment of amyloid precursor protein, a concentration-dependent decrease in amyloid-β levels was observed. However, no interaction between GSAP and the C-terminal fragment of amyloid precursor protein was evident in co-immunoprecipitation studies. In addition, subchronic administration of imatinib to rats had no effect on brain amyloid-β levels. In summary, these findings suggest the roles of GSAP and imatinib in the regulation of γ-secretase activity and amyloid-β generation are uncertain.
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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.