ArticleCell reports2012
Brain-specific disruption of the eIF2α kinase PERK decreases ATF4 expression and impairs behavioral flexibility.
Article in Cell reports, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers.
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Who cites it
91 citing papers in PubMed, 143 citations in OpenAlex.
- The transcription factor C/EBPβ promotes hyperglycemia-elicited glycolysis and liver cancer progression.Nature communications · 2026Article
- Targeting endoplasmic reticulum stress and protein misfolding in schizophrenia: the emerging promise of sigma-1 receptor agonists.Psychopharmacology · 2026Review
- The PERK inhibitor GSK2606414 evokes developmental defects in zebrafish consistent with Wolcott-Rallison syndrome phenotypes.Pharmacological reports : PR · 2026Article
- Astrocytic PERK Deficiency Drives Prefrontal Circuit Dysfunction and Depressive-Like Behaviors.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Emerging roles for integrated stress response signaling in homeostasis.The FEBS journal · 2025Review
- Unravelling axonal transcriptional landscapes: insights from induced pluripotent stem cell-derived cortical neurons and implications for motor neuron degeneration.Open biology · 2025Article
- The curious interpretation of novel object recognition tests.Trends in neurosciences · 2025Review
- Single-Cell Transcriptional Profiling Reveals Cell Type-Specific Sex-Dependent Molecular Patterns of Schizophrenia.International journal of molecular sciences · 2025Article
- Defective regulation of the eIF2-eIF2B translational axis underlies depressive-like behavior in mice and correlates with major depressive disorder in humans.Translational psychiatry · 2024Article
- The integrated stress response in brain diseases: A double-edged sword for proteostasis and synapses.Current opinion in neurobiology · 2024Review
- ER stress in mouse serotonin neurons triggers a depressive phenotype alleviated by ketamine targeting eIF2α signaling.iScience · 2024Article
- The integrated stress response pathway and neuromodulator signaling in the brain: lessons learned from dystonia.The Journal of clinical investigation · 2024Review
- Protein translation: biological processes and therapeutic strategies for human diseases.Signal transduction and targeted therapy · 2024Review
- Transcriptome analysis reveals organ-specific effects of 2-deoxyglucose treatment in healthy mice.PloS one · 2024Article
- Astrocytic deletion of protein kinase R-like ER kinase (PERK) does not affect learning and memory in aged mice but worsens outcome from experimental stroke.Journal of neuroscience research · 2023Article
- Genome-wide census of ATF4 binding sites and functional profiling of trait-associated genetic variants overlapping ATF4 binding motifs.PLoS genetics · 2023Article
- Article
- Cell-type-specific translational control of spatial working memory by the cap-binding protein 4EHP.Molecular brain · 2023Article
- Reward prediction error in learning-related behaviors.Frontiers in neuroscience · 2023Review
- Protein Misfolding and Aggregation in the Brain: Common Pathogenetic Pathways in Neurodegenerative and Mental Disorders.International journal of molecular sciences · 2022Review
31 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
Translational control depends on phosphorylation of eIF2α by PKR-like ER kinase (PERK). To examine the role of PERK in cognitive function, we selectively disrupted PERK expression in the adult mouse forebrain. In the prefrontal cortex (PFC) of PERK-deficient mice, eIF2α phosphorylation and ATF4 expression were diminished and were associated with enhanced behavioral perseveration, decreased prepulse inhibition, reduced fear extinction, and impaired behavioral flexibility. Treatment with the glycine transporter inhibitor SSR504734 normalized eIF2α phosphorylation, ATF4 expression, and behavioral flexibility in PERK-deficient mice. Moreover, the expression levels of PERK and ATF4 were reduced in the frontal cortex of human patients with schizophrenia. Together, our findings reveal that PERK plays a critical role in information processing and cognitive function and that modulation of eIF2α phosphorylation and ATF4 expression may represent an effective strategy for treating behavioral inflexibility associated with several neurological disorders such as schizophrenia.
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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.