ArticleeLife2020
Small molecule cognitive enhancer reverses age-related memory decline in mice.
Article in eLife, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 papers, 2 of them syntheses that pooled 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.
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.
Who cites it
98 citing papers in PubMed, 2 syntheses or guidelines pooled it, 167 citations in OpenAlex.
- A systematic review of the therapeutic potential of nicotinamide adenine dinucleotide precursors for cognitive diseases in preclinical rodent models.BMC neuroscience · 2025Pooled it
- Risk factors for postoperative delirium in elderly urological patients: A meta-analysis.Medicine · 2022Pooled it
- Investigational eIF2B activator DNL343 modulates the integrated stress response in preclinical models of TDP-43 pathology and individuals with ALS in a randomized clinical trial.Nature communications · 2025Trial
- Monovalent Nondegrading Molecular Glues: An Updated Overview of Emerging Mechanisms and Therapeutic Development.Pharmaceuticals (Basel, Switzerland) · 2026Review
- A massively parallel CRISPR-based screening platform for modifiers of neuronal depolarization.Nature communications · 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
- TNF-α induces type I IFN signalling to suppress neurogenesis and recruit T cells.Nature communications · 2026Article
- Atypical Tetracyclines Promote Longevity and Ferroptotic Neuroprotection via Translation Attenuation.Aging cell · 2026Article
- Extension of lifespan by epicatechin, halofuginone and mitoglitazone in male but not female genetically heterogeneous mice.GeroScience · 2026Article
- Progenitor Resilience and the Early Onset of Chronic Lung Diseases: NHLBI workshop report.American journal of respiratory cell and molecular biology · 2026Article
- Integrated stress response inhibition rescues inflammation-associated accelerated forgetting of recognition memory in mice.Psychopharmacology · 2026Article
- Atypical tetracyclines promote longevity and ferroptotic neuroprotection via translation attenuation.bioRxiv : the preprint server for biology · 2026Article
- Adaptive inter-tissue proteostasis networks in aging and neurodegeneration.Bioscience reports · 2026Review
- Directional Modulation of the Integrated Stress Response in Neurodegeneration: A Systematic Review of eIF2B Activators, PERK-Pathway Agents, and ISR Prolongers.Biomedicines · 2026Review
- Dysregulated mRNA Translation in Alzheimer's Disease: Mechanisms, Therapeutic Opportunities, and Challenges for Clinical Translation.Clinical interventions in aging · 2026Review
- The Yin-Yang of Stress and Senescence: Integrated Stress Response and SASP Crosstalk in Stem Cell Fate, Regeneration, and Disease.Biocell : official journal of the Sociedades Latinoamericanas de Microscopia Electronica ... et. al · 2026Article
- Arsenic Trioxide Underpins Delayed Neuroinflammation and Impaired Synaptic Integrity involving Integrative Stress Response Signaling.bioRxiv : the preprint server for biology · 2025Article
- Intra-tumoral hypoxia promotes CD8Immunity · 2025Article
- Overactivation of PERK-Mediated Endoplasmic Reticulum Stress-Induced Testis Damage in Chronically Stressed Mice.ACS omega · 2025Article
- Translational regulation in stress biology.Nature cell biology · 2025Review
38 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
With increased life expectancy, age-associated cognitive decline becomes a growing concern, even in the absence of recognizable neurodegenerative disease. The integrated stress response (ISR) is activated during aging and contributes to age-related brain phenotypes. We demonstrate that treatment with the drug-like small-molecule ISR inhibitor ISRIB reverses ISR activation in the brain, as indicated by decreased levels of activating transcription factor 4 (ATF4) and phosphorylated eukaryotic translation initiation factor eIF2. Furthermore, ISRIB treatment reverses spatial memory deficits and ameliorates working memory in old mice. At the cellular level in the hippocampus, ISR inhibition (i) rescues intrinsic neuronal electrophysiological properties, (ii) restores spine density and (iii) reduces immune profiles, specifically interferon and T cell-mediated responses. Thus, pharmacological interference with the ISR emerges as a promising intervention strategy for combating age-related cognitive decline in otherwise healthy individuals.
Indexed as
Identifiers
What OpenQuestion holds
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.