ArticleNeurobiology of aging2021
Suppression of the kinase for elongation factor 2 alleviates mGluR-LTD impairments in a mouse model of Alzheimer's disease.
Article in Neurobiology of aging, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 57 citations in OpenAlex.
- Betulinaldehyde Ameliorates Aβ-Induced Neurotoxicity and Cognitive Deficits by Modulating the eEF2K/eEF2 Pathway.CNS neuroscience & therapeutics · 2026Article
- Metabotropic Glutamate Receptor-Dependent Synaptic Plasticity in Age-Related Neurodegenerative Disorders.Neural plasticity · 2026Review
- Deep Hypothermic Low Flow Results in Multiple Aspects of Neurological Deficits in Mice by eEF2 Hyperphosphorylation.Molecular neurobiology · 2025Article
- Reduction of eEF2 kinase alleviates the learning and memory impairment caused by acrylamide.Cell & bioscience · 2024Article
- Isoform-specific effects of neuronal inhibition of AMPK catalytic subunit on LTD impairments in a mouse model of Alzheimer's disease.Neurobiology of aging · 2024Article
- Transcriptomic analysis reveals the crosstalk between type 2 diabetes and chronic pancreatitis.Health science reports · 2024Article
- Amyloid-βiScience · 2023Article
- Roles of eukaryotic elongation factor 2 kinase (eEF2K) in neuronal plasticity, cognition, and Alzheimer disease.Journal of neurochemistry · 2023Review
- Structure of the complex between calmodulin and a functional construct of eukaryotic elongation factor 2 kinase bound to an ATP-competitive inhibitor.The Journal of biological chemistry · 2023Article
- ADP enhances the allosteric activation of eukaryotic elongation factor 2 kinase by calmodulin.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Article
- mGluR-dependent plasticity in rodent models of Alzheimer's disease.Frontiers in synaptic neuroscience · 2023Article
- eEF2 in the prefrontal cortex promotes excitatory synaptic transmission and social novelty behavior.EMBO reports · 2022Article
- Bioactive human Alzheimer brain soluble Aβ: pathophysiology and therapeutic opportunities.Molecular psychiatry · 2022Review
- Structural basis for the calmodulin-mediated activation of eukaryotic elongation factor 2 kinase.Science advances · 2022Article
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Authors and funding
4 authors at 2 institutions in 1 country.
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Abstract
Impaired mRNA translation (protein synthesis) is linked to Alzheimer's disease (AD) pathophysiology. Recent studies revealed the role of increased phosphorylation of eukaryotic elongation factor 2 (eEF2) in AD-associated cognitive deficits. Phosphorylation of eEF2 (at the Thr56 site) by its only known kinase eEF2K leads to inhibition of general protein synthesis. AD is considered as a disease of "synaptic failure" characterized by impairments of synaptic plasticity, including long-term potentiation (LTP) and long-term depression (LTD). Deficiency of metabotropic glutamate receptor 5-dependent LTD (mGluR-LTD) is indicated in cognitive syndromes associated with various neurological disorders, including AD, but the molecular signaling mechanisms underlying the mGluR-LTD dysregulation in AD remain unclear. In this brief communication, we report genetic repression of eEF2K in aged APP/PS1 AD model mice prevented AD-associated hippocampal mGluR-LTD deficits. Using a pharmacological approach, we further observed that impairments of mGluR-LTD in APP/PS1 mice were rescued by treating hippocampal slices with a small molecule eEF2K antagonist NH125. Our findings, taken together, suggest a critical role of abnormal protein synthesis dysregulation at the elongation phase in AD-associated mGluR-LTD failure, thus providing insights into a mechanistic understanding of synaptic impairments in AD and other related dementia syndromes.
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