ArticleAging cell2016
O-GlcNAcylation of protein kinase A catalytic subunits enhances its activity: a mechanism linked to learning and memory deficits in Alzheimer's disease.
Article in Aging cell, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 88 citations in OpenAlex.
- O-GlcNAcylation as a Metabolic Integrator in Cardiovascular Physiology and Disease.International journal of molecular sciences · 2026Review
- Regulatory mechanism of O-linked N-acetylglucosamine protein modification on autophagy in cancer.Clinical and translational medicine · 2026Review
- Protein O-GlcNAcylation in Health and Diseases.MedComm · 2025Review
- Targeting O-GlcNAcylation: Novel Therapeutic Strategies for Neurological Disease.Molecular neurobiology · 2025Review
- The Glyco-Switch of life: O-GlcNAcylation in cell fate decision.Glycobiology · 2025Review
- Associations between chemoradiotherapy-based immune checkpoint blockade and posttreatment depression and anxiety in head and neck cancer patients: a cross-sectional study.Frontiers in immunology · 2025Article
- The O-GlcNAc dichotomy: when does adaptation become pathological?Clinical science (London, England : 1979) · 2023Review
- Ogt-mediated O-GlcNAcylation inhibits astrocytes activation through modulating NF-κB signaling pathway.Journal of neuroinflammation · 2023Article
- Liuwei Dihuang formula ameliorates chronic stress-induced emotional and cognitive impairments in mice by elevating hippocampal O-GlcNAc modification.Frontiers in neuroscience · 2023Article
- miR-200a-3p Regulates PRKACB and Participates in Aluminium-Induced Tau Phosphorylation in PC12 Cells.Neurotoxicity research · 2022Article
- Review
- Methods for Studying Site-Specific O-GlcNAc Modifications: Successes, Limitations, and Important Future Goals.JACS Au · 2022Review
- O-GlcNAcylation Is Essential for Rapid Pomc Expression and Cell Proliferation in Corticotropic Tumor Cells.Endocrinology · 2021Article
- REM Sleep Deprivation Impairs Learning and Memory by Decreasing Brain O-GlcNAc Cycling in Mouse.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2021Article
- O-GlcNAcylation: the "stress and nutrition receptor" in cell stress response.Cell stress & chaperones · 2021Review
- Phosphorylation andFrontiers in molecular neuroscience · 2021Article
- Article
- Increased O-GlcNAcylation induces myocardial hypertrophy.In vitro cellular & developmental biology. Animal · 2020Article
- Central and Peripheral Metabolic Defects Contribute to the Pathogenesis of Alzheimer's Disease: Targeting Mitochondria for Diagnosis and Prevention.Antioxidants & redox signaling · 2020Review
- The O-GlcNAc Modification on Kinases.ACS chemical biology · 2020Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Alzheimer's disease (AD) is characterized clinically by memory loss and cognitive decline. Protein kinase A (PKA)-CREB signaling plays a critical role in learning and memory. It is known that glucose uptake and O-GlcNAcylation are reduced in AD brain. In this study, we found that PKA catalytic subunits (PKAcs) were posttranslationally modified by O-linked N-acetylglucosamine (O-GlcNAc). O-GlcNAcylation regulated the subcellular location of PKAcα and PKAcβ and enhanced their kinase activity. Upregulation of O-GlcNAcylation in metabolically active rat brain slices by O-(2-acetamido-2-deoxy-d-glucopyranosylidenamino) N-phenylcarbamate (PUGNAc), an inhibitor of N-acetylglucosaminidase, increased the phosphorylation of tau at the PKA site, Ser214, but not at the non-PKA site, Thr205. In contrast, in rat and mouse brains, downregulation of O-GlcNAcylation caused decreases in the phosphorylation of CREB at Ser133 and of tau at Ser214, but not at Thr205. Reduction in O-GlcNAcylation through intracerebroventricular injection of 6-diazo-5-oxo-l-norleucine (DON), the inhibitor of glutamine fructose-6-phosphate amidotransferase, suppressed PKA-CREB signaling and impaired learning and memory in mice. These results indicate that in addition to cAMP and phosphorylation, O-GlcNAcylation is a novel mechanism that regulates PKA-CREB signaling. Downregulation of O-GlcNAcylation suppresses PKA-CREB signaling and consequently causes learning and memory deficits in AD.
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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.