ArticleeLife2019
eIF2B activator prevents neurological defects caused by a chronic integrated stress response.
Article in eLife, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 149 papers.
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Who cites it
149 citing papers in PubMed, 216 citations in OpenAlex.
- DNL343 and Disease Progression in Amyotrophic Lateral Sclerosis: A Randomized Clinical Trial.JAMA network open · 2026Trial
- 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
- White matter disorders at the intersection of transcription, RNA processing and translation.Nature reviews. Neurology · 2026Review
- Integrated stress response activation in combination PG3 and cisplatin-treatedbioRxiv : the preprint server for biology · 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
- MDA5 and the integrated stress response control sex-specific type 1 diabetes onset in NOD mice.bioRxiv : the preprint server for biology · 2026Article
- Article
- YAP-activated lymph node fibroblasts contribute to extracellular matrix remodeling associated with extranodal extension of oral squamous cell carcinoma.The journal of pathology. Clinical research · 2026Article
- Allosteric disordering of eIF2B regulates the integrated stress response.Nature chemical biology · 2026Article
- Therapeutic targeting of the eIF4E cap-binding domain reveals control of lineage fate in prostate cancer.The Journal of clinical investigation · 2026Article
- AMC-F1 regulates mitochondria-autophagy crosstalk independent of nutrient stress.Nature communications · 2026Article
- Cardiolipin preserves TNature metabolism · 2026Article
- Progenitor Resilience and the Early Onset of Chronic Lung Diseases: NHLBI workshop report.American journal of respiratory cell and molecular biology · 2026Article
- A molecular stabiliser of an inhibitory eIF2B-eIF2(αP) complex activates the Integrated Stress Response.Nature communications · 2026Article
- Disruption of CSF-1 receptor-mediated metal ion homeostasis in the murine brain promotes neurodegenerative disease.The Journal of clinical investigation · 2026Article
- RK-33 inhibits the OC43 coronavirus and induces stress granules via DDX3X-independent mechanisms.RNA (New York, N.Y.) · 2026Article
- Integrated stress response inhibition rescues inflammation-associated accelerated forgetting of recognition memory in mice.Psychopharmacology · 2026Article
- EMC3 as a Novel Biomarker and Driver of PI3K/AKT/mTOR Signaling in Hepatocellular Carcinoma Progression.Annals of surgical oncology · 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
- Directional Modulation of the Integrated Stress Response in Neurodegeneration: A Systematic Review of eIF2B Activators, PERK-Pathway Agents, and ISR Prolongers.Biomedicines · 2026Review
89 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
22 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The integrated stress response (ISR) attenuates the rate of protein synthesis while inducing expression of stress proteins in cells. Various insults activate kinases that phosphorylate the GTPase eIF2 leading to inhibition of its exchange factor eIF2B. Vanishing White Matter (VWM) is a neurological disease caused by eIF2B mutations that, like phosphorylated eIF2, reduce its activity. We show that introduction of a human VWM mutation into mice leads to persistent ISR induction in the central nervous system. ISR activation precedes myelin loss and development of motor deficits. Remarkably, long-term treatment with a small molecule eIF2B activator, 2BAct, prevents all measures of pathology and normalizes the transcriptome and proteome of VWM mice. 2BAct stimulates the remaining activity of mutant eIF2B complex in vivo, abrogating the maladaptive stress response. Thus, 2BAct-like molecules may provide a promising therapeutic approach for VWM and provide relief from chronic ISR induction in a variety of disease contexts.
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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.