ArticleeLife2021
Prolonging the integrated stress response enhances CNS remyelination in an inflammatory environment.
Article in eLife, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
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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.
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.
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Who cites it
27 citing papers in PubMed, 36 citations in OpenAlex.
- Article
- Modulation of the unfolded protein response with a C-terminal fragment of MANF facilitates recovery in models of multiple sclerosis.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Autophagy-NLRP3 Inflammasome Crosstalk in Microglia: A Therapeutic Target for Multiple Sclerosis.Inflammation · 2026Review
- T cell-microglial interactions that impair myelin maintenance and regeneration: cellular mechanisms on white-matter associated changes.Frontiers in immunology · 2026Review
- Therapeutic targeting of oligodendrocytes in an agent-based model of multiple sclerosis.PLoS computational biology · 2026Article
- Pharmacological targeting of RIG-I can selectively activate the integrated stress response.Science advances · 2025Article
- Review
- Review
- The integrated stress response in neurodegenerative diseases.Molecular neurodegeneration · 2025Review
- GCN2-Mediated eIF2α Phosphorylation Is Required for Central Nervous System Remyelination.International journal of molecular sciences · 2025Article
- Restore axonal conductance in a locally demyelinated axon with electromagnetic stimulation.Journal of neural engineering · 2025Article
- ISR Modulators in Neurological Diseases.Current neuropharmacology · 2025Review
- Review
- Navigating the Landscape of CMT1B: Understanding Genetic Pathways, Disease Models, and Potential Therapeutic Approaches.International journal of molecular sciences · 2024Review
- Interferon-γ controls aquaporin 4-specific Th17 and B cells in neuromyelitis optica spectrum disorder.Brain : a journal of neurology · 2024Article
- Article
- Developing Hypoimmunogenic Human iPSC-Derived Oligodendrocyte Progenitor Cells as an Off-The-Shelf Cell Therapy for Myelin Disorders.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- NF-κB is a critical mediator of post-mitotic senescence in oligodendrocytes and subsequent white matter loss.Molecular neurodegeneration · 2023Article
- Targeting protein phosphatases in cancer immunotherapy and autoimmune disorders.Nature reviews. Drug discovery · 2023Review
- Insights into the mechanism of oligodendrocyte protection and remyelination enhancement by the integrated stress response.bioRxiv : the preprint server for biology · 2023Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The inflammatory environment of demyelinated lesions in multiple sclerosis (MS) patients contributes to remyelination failure. Inflammation activates a cytoprotective pathway, the integrated stress response (ISR), but it remains unclear whether enhancing the ISR can improve remyelination in an inflammatory environment. To examine this possibility, the remyelination stage of experimental autoimmune encephalomyelitis (EAE), as well as a mouse model that incorporates cuprizone-induced demyelination along with CNS delivery of the proinflammatory cytokine IFN-γ were used here. We demonstrate that either genetic or pharmacological ISR enhancement significantly increased the number of remyelinating oligodendrocytes and remyelinated axons in the inflammatory lesions. Moreover, the combined treatment of the ISR modulator Sephin1 with the oligodendrocyte differentiation enhancing reagent bazedoxifene increased myelin thickness of remyelinated axons to pre-lesion levels. Taken together, our findings indicate that prolonging the ISR protects remyelinating oligodendrocytes and promotes remyelination in the presence of inflammation, suggesting that ISR enhancement may provide reparative benefit to MS patients.
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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.