ArticleFrontiers in aging neuroscience2017
Reducing the Levels of Akt Activation by PDK1 Knock-in Mutation Protects Neuronal Cultures against Synthetic Amyloid-Beta Peptides.
Article in Frontiers in aging neuroscience, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 39 citations in OpenAlex.
- GPR146 Deficiency Enhances Microglial Phagocytosis and Blood-Brain Barrier-Associated Markers in an Acute Amyloid-β Model.Molecular neurobiology · 2026Article
- Neuroinflammation in Alzheimer's disease: glial crosstalk, pathological modulation, and therapeutic implications.Frontiers in immunology · 2026Review
- Fueling the brain - the role of apolipoprotein E in brain energy metabolism and its implications for Alzheimer's disease.Translational psychiatry · 2025Review
- Identification of therapeutic targets for Alzheimer's Disease Treatment using bioinformatics and machine learning.Scientific reports · 2025Article
- Glucose Metabolic Abnormality: A Crosstalk between Depression and Alzheimer's Disease.Current neuropharmacology · 2025Review
- CD87-targeted BiTE and CAR-T cells potently inhibit invasive nonfunctional pituitary adenomas.Science China. Life sciences · 2024Article
- Tyrosine phosphorylation and palmitoylation of TRPV2 ion channel tune microglial beta-amyloid peptide phagocytosis.Journal of neuroinflammation · 2024Article
- Aging and putative frailty biomarkers are altered by spaceflight.Scientific reports · 2024Article
- Article
- Reducing PDK1/Akt Activity: An Effective Therapeutic Target in the Treatment of Alzheimer's Disease.Cells · 2022Review
- Article
- uPAR: An Essential Factor for Tumor Development.Journal of Cancer · 2021Review
- The Cellular Prion Protein-ROCK Connection: Contribution to Neuronal Homeostasis and Neurodegenerative Diseases.Frontiers in cellular neuroscience · 2021Review
- Neuronostatin Promotion Soluble Aβ1-42 Oligomers: Induced Dysfunctional Brain Glucose Metabolism in Mice.Neurochemical research · 2020Article
- Sulfhydration of AKT triggers Tau-phosphorylation by activating glycogen synthase kinase 3β in Alzheimer's disease.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Article
- The Impact of the PI3K/Akt Signaling Pathway in Anxiety and Working Memory in Young and Middle-Aged PDK1 K465E Knock-In Mice.Frontiers in behavioral neuroscience · 2020Article
- Production of seedable Amyloid-β peptides in model of prion diseases upon PrPNature communications · 2019Article
- Aging-induced Akt activation involves in aging-related pathologies and Aβ-induced toxicity.Aging cell · 2019Article
- The Neuroprotection of KIBRA in Promoting Neuron Survival and Against Amyloid β-Induced Apoptosis.Frontiers in cellular neuroscience · 2019Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Akt kinase has been widely assumed for years as a key downstream effector of the PI3K signaling pathway in promoting neuronal survival. This notion was however challenged by the finding that neuronal survival responses were still preserved in mice with reduced Akt activity. Moreover, here we show that the Akt signaling is elevated in the aged brain of two different mice models of Alzheimer Disease. We manipulate the rate of Akt stimulation by employing knock-in mice expressing a mutant form of PDK1 (phosphoinositide-dependent protein kinase 1) with reduced, but not abolished, ability to activate Akt. We found increased membrane localization and activity of the TACE/ADAM17 α-secretase in the brain of the PDK1 mutant mice with concomitant TNFR1 processing, which provided neurons with resistance against TNFα-induced neurotoxicity. Opposite to the Alzheimer Disease transgenic mice, the PDK1 knock-in mice exhibited an age-dependent attenuation of the unfolding protein response, which protected the mutant neurons against endoplasmic reticulum stressors. Moreover, these two mechanisms cooperatively provide the mutant neurons with resistance against amyloid-beta oligomers, and might singularly also contribute to protect these mice against amyloid-beta pathology.
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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 OpenQuestion graph.