ArticleScience (New York, N.Y.)2019
Activation of the ISR mediates the behavioral and neurophysiological abnormalities in Down syndrome.
Article in Science (New York, N.Y.), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 106 papers.
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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.
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Who cites it
106 citing papers in PubMed, 181 citations in OpenAlex.
- Error-prone translation as a driver of proteostasis collapse and neurodegeneration.Neural regeneration research · 2026Article
- Monovalent Nondegrading Molecular Glues: An Updated Overview of Emerging Mechanisms and Therapeutic Development.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Twenty-Five Years of the Environmental Stress Response and the Enduring Power of Yeast in Stress Biology.Yeast (Chichester, England) · 2026Review
- 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
- Impaired Activity-Regulated Proteostasis: A Shared Mechanism in Neurodevelopmental Disorders.Biological psychiatry · 2026Review
- Structural Transformation of a BRAF Inhibitor into a Selective PKR Inhibitor.Journal of medicinal chemistry · 2026Article
- Allosteric disordering of eIF2B regulates the integrated stress response.Nature chemical biology · 2026Article
- Loss of Proteostasis and Early-Onset Neurodegeneration in Down Syndrome: From Mechanisms to Interventions.Antioxidants (Basel, Switzerland) · 2026Review
- Interplay between DYRK1A dosage and aneuploidy-induced neuropathology in Down syndrome.Communications biology · 2026Article
- Sleep Maintenance Insomnia in Older Adults: Cardiometabolic Comorbidities and Evidence of Antiviral Pathways Activation from Blood Transcriptome and dsRNA Expression Analyses.International journal of molecular sciences · 2026Article
- Function and regulation of the mitochondrial stress response.Nature structural & molecular biology · 2026Review
- 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
- Inhibition of integrated stress response by ISRIB promotes mouse and human primordial follicle activation via the mTOR pathway.Journal of assisted reproduction and genetics · 2025Article
- A retrograde, non-canonical integrated stress response cascade maintains synaptic strength under amino acid deprivation.Cell reports · 2025Article
- TUSC3 regulates ERMA-mediated MgNature communications · 2025Article
- Molecular cartography of the human down syndrome and trisomic mouse brain.Nature communications · 2025Article
- Restoring glucose metabolism in Alzheimer's disease by targeting integrated stress response.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Article
- Ripply3 overdosage induces mid-face shortening through Tbx1 downregulation in Down syndrome models.PLoS genetics · 2025Article
- Dual Nature of Mitochondrial Integrated Stress Response: Molecular Switches from Protection to Pathology.Genes · 2025Review
- Aneuploidy-induced proteostasis disruption impairs mitochondrial functions and mediates aggregation of mitochondrial precursor proteins through SQSTM1/p62.Nature communications · 2025Article
46 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Down syndrome (DS) is the most common genetic cause of intellectual disability. Protein homeostasis is essential for normal brain function, but little is known about its role in DS pathophysiology. In this study, we found that the integrated stress response (ISR)-a signaling network that maintains proteostasis-was activated in the brains of DS mice and individuals with DS, reprogramming translation. Genetic and pharmacological suppression of the ISR, by inhibiting the ISR-inducing double-stranded RNA-activated protein kinase or boosting the function of the eukaryotic translation initiation factor eIF2-eIF2B complex, reversed the changes in translation and inhibitory synaptic transmission and rescued the synaptic plasticity and long-term memory deficits in DS mice. Thus, the ISR plays a crucial role in DS, which suggests that tuning of the ISR may provide a promising therapeutic intervention.
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Registered trials
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.