Evidence map›Paper›PMID 33341653›Full record

ArticleNeurobiology of aging2021

Suppression of the kinase for elongation factor 2 alleviates mGluR-LTD impairments in a mouse model of Alzheimer's disease.

Wenzhong Yang, Xueyan Zhou, Alexey G Ryazanov, Tao Ma

Open access · greenAbstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.4field-weighted citation impact, top 18% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

15 citing papers in PubMed, 57 citations in OpenAlex.

  1. Article
  2. Review
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  7. Amyloid-βiScience · 2023
    Article
  8. Review
  9. Article
  10. 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 · 2023
    Article
  11. Article
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  14. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 2 institutions in 1 country.

Wenzhong YangDepartment of Internal Medicine-Gerontology and Geriatric Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
Xueyan ZhouDepartment of Internal Medicine-Gerontology and Geriatric Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
Alexey G RyazanovDepartment of Pharmacology, Robert Wood Johnson Medical School, Rutgers University, Piscataway, NJ, USA.
Tao MaDepartment of Internal Medicine-Gerontology and Geriatric Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, USA; Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, NC, USA; Department of Neurobiology and Anatomy, Wake Forest University School of Medicine, Winston-Salem, NC, USA. Electronic address: tma@wakehealth.edu.
Wake Forest University · USJohnson University · US

Funding

Isoform-specific roles of AMPK in synaptic failure and memory deficit in Alzheimer's DiseaseR01AG055581 · NIA · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI MA, TAO · 2017 to 2021
$2.9M
Role of protein synthesis in Alzheimers disease-associated impairments of synaptic plasticity and memoryR01AG056622 · NIA · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI MA, TAO · 2017 to 2021
$2.4M
NIA NIH HHS R01 AG055581NIA NIH HHS R01 AG056622
6 · The paper itself

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.

Indexed as

Alzheimer DiseaseAnimalsDisease Models, AnimalHippocampusImidazolesLong-Term PotentiationMice, TransgenicNeuronal PlasticityPeptide Elongation Factor 2PhosphorylationProtein BiosynthesisReceptor, Metabotropic Glutamate 5ImidazolesNH 125Peptide Elongation Factor 2Receptor, Metabotropic Glutamate 5Alzheimer’s diseaseeEF2KmGluR-LTDProtein synthesisSynaptic plasticity

Identifiers

PMID33341653
PMCPMC8201868
OpenAlexW3107747402

What Socratic holds

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Read underepoch 390

Registered trials

None linked

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.