ArticleThe EMBO journal2004
PS1 activates PI3K thus inhibiting GSK-3 activity and tau overphosphorylation: effects of FAD mutations.
Article in The EMBO journal, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 116 papers.
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Who cites it
116 citing papers in PubMed, 287 citations in OpenAlex.
- The Synergistic Role of ApoE4 and GSK3β in Alzheimer's Disease: Pathological Mechanisms and Therapeutic Implications.Molecular neurobiology · 2025Review
- Neuroprotective effect of Tozasertib in Streptozotocin-induced alzheimer's mice model.Scientific reports · 2025Article
- Protein kinases in neurodegenerative diseases: current understandings and implications for drug discovery.Signal transduction and targeted therapy · 2025Review
- Glycogen synthase kinase 3 (GSK3) inhibition: a potential therapeutic strategy for Alzheimer's disease.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Review
- BMAL1 ameliorates type 2 diabetes-induced cognitive impairment via AREG upregulation and PI3K/Akt/GSK-3β pathway activation.Cell communication and signaling : CCS · 2025Article
- Allocryptopine, tetrahydropalmatine, and tetrahydroberberine N-oxide alkaloids alleviate cellular stress by modulating calcium homeostasis and the MAPK and akt/GSK-3β/tau signaling pathways.Frontiers in pharmacology · 2025Article
- Updates in Alzheimer's disease: from basic research to diagnosis and therapies.Translational neurodegeneration · 2024Review
- A High-Carbohydrate Diet Induces Cognitive Impairment and Promotes Amyloid Burden and Tau Phosphorylation via PI3K/Akt/GSK-3β Pathway in db/db Mice.Biomedicines · 2024Article
- 1-Deoxynojirimycin attenuates pathological markers of Alzheimer's disease in the in vitro model of neuronal insulin resistance.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- The role of PI3K signaling pathway in Alzheimer's disease.Frontiers in aging neuroscience · 2024Review
- Presenilin-1 (PSEN1) Mutations: Clinical Phenotypes beyond Alzheimer's Disease.International journal of molecular sciences · 2023Review
- Ginsenoside F2 enhances glucose metabolism by modulating insulin signal transduction in human hepatocarcinoma cells.Journal of ginseng research · 2023Article
- Shared miRNA landscapes of COVID-19 and neurodegeneration confirm neuroinflammation as an important overlapping feature.Frontiers in molecular neuroscience · 2023Article
- Glycosylated clusterin species facilitate Aβ toxicity in human neurons.Scientific reports · 2022Article
- In Vitro Anti-Proliferative and Apoptotic Effects of Hydroxytyrosyl Oleate on SH-SY5Y Human Neuroblastoma Cells.International journal of molecular sciences · 2022Article
- The attenuation effect of potassium 2-(1-hydroxypentyl)-benzoate in a mouse model of diabetes-associated cognitive decline: The protein expression in the brain.CNS neuroscience & therapeutics · 2022Article
- Article
- Implications of Phosphoinositide 3-Kinase-Akt (PI3K-Akt) Pathway in the Pathogenesis of Alzheimer's Disease.Molecular neurobiology · 2022Review
- CHIP promotes Wnt signaling and regulates Arc stability by recruiting and polyubiquitinating LEF1 or Arc.Cell death discovery · 2021Article
56 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Phosphatidylinositol 3-kinase (PI3K) promotes cell survival and communication by activating its downstream effector Akt kinase. Here we show that PS1, a protein involved in familial Alzheimer's disease (FAD), promotes cell survival by activating the PI3K/Akt cell survival signaling. This function of PS1 is unaffected by gamma-secretase inhibitors. Pharmacological and genetic evidence indicates that PS1 acts upstream of Akt, at or before PI3K kinase. PS1 forms complexes with the p85 subunit of PI3K and promotes cadherin/PI3K association. Furthermore, conditions that inhibit this association prevent the PS1-induced PI3K/Akt activation, indicating that PS1 stimulates PI3K/Akt signaling by promoting cadherin/PI3K association. By activating PI3K/Akt signaling, PS1 promotes phosphorylation/inactivation of glycogen synthase kinase-3 (GSK-3), suppresses GSK-3-dependent phosphorylation of tau at residues overphosphorylated in AD and prevents apoptosis of confluent cells. PS1 FAD mutations inhibit the PS1-dependent PI3K/Akt activation, thus promoting GSK-3 activity and tau overphosphorylation at AD-related residues. Our data raise the possibility that PS1 may prevent development of AD pathology by activating the PI3K/Akt signaling pathway. In contrast, FAD mutations may promote AD pathology by inhibiting this pathway.
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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.