ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2013
Oligodendrocyte-specific activation of PERK signaling protects mice against experimental autoimmune encephalomyelitis.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2013. 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 78 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
78 citing papers in PubMed, 111 citations in OpenAlex.
- S3I-201, a STAT3 Inhibitor, Inhibits Proinflammatory Mediator Signalling in CD19 and CD45R/B220 Cells in a Mouse Model of Multiple Sclerosis.Cellular and molecular neurobiology · 2026Article
- PERK Deficiency Amplifies Molecular, Structural, and Network Vulnerability to Repetitive Mild Traumatic Brain Injury.bioRxiv : the preprint server for biology · 2026Article
- Oligodendrocytes Are Active Participants in the Pathogenesis of Multiple Sclerosis and Its Animal Models.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
- The integrated stress response in neurodegenerative diseases.Molecular neurodegeneration · 2025Review
- Endoplasmic reticulum's role in multiple sclerosis, exploring potential biomarkers, and pioneering therapeutic strategies: a comprehensive review of literature.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025Review
- Stem cell activity shapes the pleiotropic effects of IFN-γ and TGF-β in autoimmune diseases, infections, and cancer, and drives autoimmune flares and remissions.Frontiers in immunology · 2025Review
- Thinning of originally-existing, mature myelin represents a nondestructive form of myelin loss in the adult CNS.Frontiers in cellular neuroscience · 2025Article
- Overview of emerging therapies for demyelinating diseases.World journal of clinical cases · 2024Review
- Article
- Mechanisms Governing Oligodendrocyte Viability in Multiple Sclerosis and Its Animal Models.Cells · 2024Review
- Reduced Expression of Oligodendrocyte Linage-Enriched Transcripts During the Endoplasmic Reticulum Stress/Integrated Stress Response.ASN neuro · 2024Article
- CD44 correlates with longevity and enhances basal ATF6 activity and ER stress resistance.Cell reports · 2023Article
- Article
- The PERK pathway: beneficial or detrimental for neurodegenerative diseases and tumor growth and cancer.Human molecular genetics · 2023Review
- DAPTA, a C-C Chemokine Receptor 5 (CCR5), Leads to the Downregulation of Notch/NF-κB Signaling and Proinflammatory Mediators in CD40Biomedicines · 2023Article
- Involvement of Degenerating 21.5 kDa Isoform of Myelin Basic Protein in the Pathogenesis of the Relapse in Murine Relapsing-Remitting Experimental Autoimmune Encephalomyelitis and MS Autopsied Brain.International journal of molecular sciences · 2023Article
- Detection of PERK Signaling in the Central Nervous System.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Establishment of chemically oligomerizable TAR DNA-binding protein-43 which mimics amyotrophic lateral sclerosis pathology in mammalian cells.Laboratory investigation; a journal of technical methods and pathology · 2021Article
- Article
18 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
10 authors at 5 institutions in 3 countries.
Funding
Abstract
There is compelling evidence that oligodendrocyte apoptosis, in response to CNS inflammation, contributes significantly to the development of the demyelinating disorder multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE). Therefore, approaches designed to protect oligodendrocytes would likely have therapeutic value. Activation of pancreatic endoplasmic reticulum kinase (PERK) signaling in response to endoplasmic reticulum (ER) stress increases cell survival under various cytotoxic conditions. Moreover, there is evidence that PERK signaling is activated in oligodendrocytes within demyelinating lesions in multiple sclerosis and EAE. Our previous study demonstrated that CNS delivery of the inflammatory cytokine interferon-γ before EAE onset protected mice against EAE, and this protection was dependent on PERK signaling. In our current study, we sought to elucidate the role of PERK signaling in oligodendrocytes during EAE. We generated transgenic mice that allow for temporally controlled activation of PERK signaling, in the absence of ER stress, specifically in oligodendrocytes. We demonstrated that persistent activation of PERK signaling was not deleterious to oligodendrocyte viability or the myelin of adult animals. Importantly, we found that enhanced activation of PERK signaling specifically in oligodendrocytes significantly attenuated EAE disease severity, which was associated with reduced oligodendrocyte apoptosis, demyelination, and axonal degeneration. This effect was not the result of an altered degree of the inflammatory response in EAE mice. Our results provide direct evidence that activation of PERK signaling in oligodendrocytes is cytoprotective, protecting mice against EAE.
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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.