ArticleNature neuroscience2013
Suppression of eIF2α kinases alleviates Alzheimer's disease-related plasticity and memory deficits.
Article in Nature neuroscience, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 338 papers, 1 of them a synthesis that pooled it.
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Who cites it
338 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Cross-tissue analysis of blood and brain epigenome-wide association studies in Alzheimer's disease.Nature communications · 2022Pooled it
- Fyn kinase: a key mechanistic regulator and therapeutic target in tauopathy and neurodegenerative diseases.Translational neurodegeneration · 2026Review
- The Drosophila CEBPG homolog Irbp18 partners with crc (ATF4) to mediate the integrated stress response in degenerative disease models.Cell reports · 2026Article
- Distinct cell type-specific mechanisms underlie cognitive dysfunction during persistent integrated stress response activation.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Suppression of neuronal p27 impairs cognitive function in middle-aged mice.Neurobiology of disease · 2026Article
- Allosteric disordering of eIF2B regulates the integrated stress response.Nature chemical biology · 2026Article
- Targeting the integrated stress response or Ataxin-2 alleviates neurodegeneration in PolyGR models of C9orf72 associated frontotemporal dementia and amyotrophic lateral sclerosis.Acta neuropathologica communications · 2026Article
- Overactive Neuronal eEF2K/eEF2 signaling is associated with cognitive impairment and apathy-like behavior.Molecular psychiatry · 2026Article
- Loss of Proteostasis and Early-Onset Neurodegeneration in Down Syndrome: From Mechanisms to Interventions.Antioxidants (Basel, Switzerland) · 2026Review
- Single-cell sequencing combined with transcriptome sequencing to reveal the molecular mechanisms related to integrated stress responses in atherosclerosis.Journal of cardiothoracic surgery · 2026Article
- Neurons with granulovacuolar degeneration bodies are resilient to tau-induced protein synthesis impairment.Science advances · 2026Article
- Review
- Structural basis for pseudokinase-mediated regulation of GCN2 in the integrated stress response.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Therapeutic Options for Alzheimer's Disease and Aging-Associated Cognitive Decline: State of the Art in the ACH2.0 Paradigm.International journal of molecular sciences · 2026Review
- Astrocytic PERK Deficiency Drives Prefrontal Circuit Dysfunction and Depressive-Like Behaviors.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The Muscle-Brain Axis in Aging: Mechanistic and Clinical Perspectives on Resistance Training and Cognitive Function.Biology · 2026Review
- Adaptive inter-tissue proteostasis networks in aging and neurodegeneration.Bioscience reports · 2026Review
- Neuroendocrine-immune perturbations in metabolic disease: pathophysiological mechanisms underlying cognitive impairment.Frontiers in human neuroscience · 2026Review
- 27-Hydroxycholesterol triggers microglial senescence subsequent to iron over-loading contributes to brain aging, suppressed by Deferoxamine.npj aging · 2025Article
- The Role and Therapeutic Potential of the cGAS-STING Signaling Pathway in Alzheimer's Disease.Brain and behavior · 2025Review
278 more citing papers are in PubMed but not listed here.
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Abstract
Expression of long-lasting synaptic plasticity and long-term memory requires protein synthesis, which can be repressed by phosphorylation of eukaryotic initiation factor 2 α-subunit (eIF2α). Elevated phosphorylation of eIF2α has been observed in the brains of Alzheimer's disease patients and Alzheimer's disease model mice. Therefore, we tested whether suppressing eIF2α kinases could alleviate synaptic plasticity and memory deficits in Alzheimer's disease model mice. Genetic deletion of eIF2α kinase PERK prevented enhanced phosphorylation of eIF2α and deficits in protein synthesis, synaptic plasticity and spatial memory in mice that express familial Alzheimer's disease-related mutations in APP and PSEN1. Similarly, deletion of another eIF2α kinase, GCN2, prevented impairments of synaptic plasticity and defects in spatial memory exhibited by the Alzheimer's disease model mice. Our findings implicate aberrant eIF2α phosphorylation as a previously unidentified molecular mechanism underlying Alzheimer's disease-related synaptic pathophysioloy and memory dysfunction and suggest that PERK and GCN2 are potential therapeutic targets for treatment of individuals with Alzheimer's disease.
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