ArticleThe American journal of pathology2008
Enhanced integrated stress response promotes myelinating oligodendrocyte survival in response to interferon-gamma.
Article in The American journal of pathology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02423083 (Phase I Study of Oral Guanabenz for Multiple Sclerosis), which is not on this map. Cited by 69 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.
Phase I Study of Oral Guanabenz for Multiple Sclerosis
Who cites it
69 citing papers in PubMed, 101 citations in OpenAlex.
- Senolytic treatment induces oligodendrocyte dysfunction and demyelination in the corpus callosum.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Therapeutic targeting of oligodendrocytes in an agent-based model of multiple sclerosis.PLoS computational biology · 2026Article
- T cell-microglial interactions that impair myelin maintenance and regeneration: cellular mechanisms on white-matter associated changes.Frontiers in immunology · 2026Review
- Integrated stress response inhibition prolongs the lifespan of a Pelizaeus-Merzbacher disease mouse model by increasing oligodendrocyte survival.Nature communications · 2025Article
- The integrated stress response in neurodegenerative diseases.Molecular neurodegeneration · 2025Review
- Interferon-γ controls aquaporin 4-specific Th17 and B cells in neuromyelitis optica spectrum disorder.Brain : a journal of neurology · 2024Article
- Mechanisms Governing Oligodendrocyte Viability in Multiple Sclerosis and Its Animal Models.Cells · 2024Review
- The PERK pathway: beneficial or detrimental for neurodegenerative diseases and tumor growth and cancer.Human molecular genetics · 2023Review
- NF-κB is a critical mediator of post-mitotic senescence in oligodendrocytes and subsequent white matter loss.Molecular neurodegeneration · 2023Article
- Immunomodulatory therapy with glatiramer acetate reduces endoplasmic reticulum stress and mitochondrial dysfunction in experimental autoimmune encephalomyelitis.Scientific reports · 2023Article
- Targeting protein phosphatases in cancer immunotherapy and autoimmune disorders.Nature reviews. Drug discovery · 2023Review
- Detection of PERK Signaling in the Central Nervous System.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Elimination of negative feedback in TLR signalling allows rapid and hypersensitive detection of microbial contaminants.Scientific reports · 2021Article
- Article
- Prolonging the integrated stress response enhances CNS remyelination in an inflammatory environment.eLife · 2021Article
- Amyotrophic Lateral Sclerosis Genes inInternational journal of molecular sciences · 2021Review
- Endoplasmic Reticulum Stress-Associated Neuronal Death and Innate Immune Response in Neurological Diseases.Frontiers in immunology · 2021Review
- Environmental Enrichment and Its Benefits for Migraine: Dendritic Cell Extracellular Vesicles as an Effective Mimetic.Journal of cellular immunology · 2021Article
- Suppressing endoplasmic reticulum stress-related autophagy attenuates retinal light injury.Aging · 2020Article
- Unfolded protein response in myelin disorders.Neural regeneration research · 2020Review
9 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
6 authors at 2 institutions in 1 country.
Funding
Abstract
The T-cell-derived, pleiotropic cytokine interferon (IFN)-gamma is believed to play a key regulatory role in immune-mediated demyelinating disorders of the central nervous system, including multiple sclerosis and experimental autoimmune encephalomyelitis. Our previous work has demonstrated that the endoplasmic reticulum (ER) stress response modulates the response of oligodendrocytes to this cytokine. The ER stress response activates the pancreatic ER kinase, which coordinates an adaptive program known as the integrated stress response by phosphorylating translation initiation factor 2alpha (eIF2alpha). In this study, we found that growth arrest and DNA damage 34 (GADD34), a stress-inducible regulatory subunit of a phosphatase complex that dephosphorylates eIF2alpha, was selectively up-regulated in myelinating oligodendrocytes in mice that ectopically expressed IFN-gamma in the central nervous system. We also found that a GADD34 mutant strain of mice displayed increased levels of phosphorylated eIF2alpha (p-eIF2alpha) in myelinating oligodendrocytes when exposure to IFN-gamma, as well as diminished oligodendrocyte loss and hypomyelination. Furthermore, treatment with salubrinal, a small chemical compound that specifically inhibits protein phosphatase 1(PP1)-GADD34 phosphatase activity, increased the levels of p-eIF2alpha and ameliorated hypomyelination and oligodendrocyte loss in cultured hippocampal slices exposed to IFN-gamma. Thus, our data provide evidence that an enhanced integrated stress response could promote oligodendrocyte survival in immune-mediated demyelination diseases.
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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.