ArticleGlia2018
Functional antagonism of sphingosine-1-phosphate receptor 1 prevents cuprizone-induced demyelination.
Article in Glia, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 2 of them syntheses that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
26 citing papers in PubMed, 2 syntheses or guidelines pooled it, 48 citations in OpenAlex.
- Effects of Sphingosine 1-phosphate Modulators on Central Remyelination: A Systematic Review of Animal Models.Cellular and molecular neurobiology · 2026Pooled it
- Current status of neuroprotective and neuroregenerative strategies in multiple sclerosis: A systematic review.Multiple sclerosis (Houndmills, Basingstoke, England) · 2022Pooled it
- Article
- Deciphering the role of sphingosine 1-phosphate in central nervous system myelination and repair.Journal of neurochemistry · 2025Review
- Augmentation of Endothelial S1PR1 Attenuates Postviral Pulmonary Fibrosis.American journal of respiratory cell and molecular biology · 2024Article
- Article
- CDP-choline to promote remyelination in multiple sclerosis: the need for a clinical trial.Neural regeneration research · 2023Review
- Astrocytes: Lessons Learned from the Cuprizone Model.International journal of molecular sciences · 2023Review
- Article
- Roles and regulation of microglia activity in multiple sclerosis: insights from animal models.Nature reviews. Neuroscience · 2023Review
- Molecular and neuroimmune pharmacology of S1P receptor modulators and other disease-modifying therapies for multiple sclerosis.Pharmacology & therapeutics · 2023Review
- Brain region dependent molecular signatures and myelin repair following chronic demyelination.Frontiers in cellular neuroscience · 2023Article
- Siponimod ameliorates metabolic oligodendrocyte injury via the sphingosine-1 phosphate receptor 5.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Article
- Therapeutic effect of combination vitamin D3 and siponimod on remyelination and modulate microglia activation in cuprizone mouse model of multiple sclerosis.Frontiers in behavioral neuroscience · 2022Article
- Siponimod (BAF312) penetrates, distributes, and acts in the central nervous system: Preclinical insights.Multiple sclerosis journal - experimental, translational and clinical · 2021Article
- Critical Roles of Lysophospholipid Receptors in Activation of Neuroglia and Their Neuroinflammatory Responses.International journal of molecular sciences · 2021Review
- Artificial intelligence and leukocyte epigenomics: Evaluation and prediction of late-onset Alzheimer's disease.PloS one · 2021Article
- AFrontiers in neuroscience · 2021Review
- Sphingosine-1-Phosphate Receptor Modulators and Oligodendroglial Cells: Beyond Immunomodulation.International journal of molecular sciences · 2020Review
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
Recent evidence suggests that the oral drug Fingolimod (FTY720) for relapsing-remitting multiple sclerosis (MS) may act directly on the central nervous system (CNS) and modulate disease pathogenesis and progression in experimental models of MS. However, the specific subtype of sphingosine-1-phosphate (S1P) receptors that mediates the effect of FTY720 on the CNS cells has not been fully elucidated. Here, we report that S1P receptor 1 (S1PR1) is elevated in reactive astrocytes in an autoimmunity independent mouse model of MS and that selective S1PR1 modulation is sufficient to ameliorate the loss of oligodendrocytes and demyelination. The non-selective S1PR modulator, FTY720, or a short-lived S1PR1-specific modulator, CYM5442, was administered daily to mice while on cuprizone diet. Both FTY720- and CYM5422-treated mice displayed a significant reduction in oligodendrocyte apoptosis and astrocyte and microglial activation in comparison to vehicle-treated groups, which was associated with decreased production of proinflammatory mediators and down-regulation of astrocytic S1PR1 protein. Interestingly, S1PR1 modulation during the early phase of cuprizone intoxication was required to suppress oligodendrocyte death and consequent demyelination as drug treatment from 10 days after the initiation of cuprizone feeding was no longer effective. CYM5442 treatment during the brief cuprizone exposure significantly prevented Il-1β, Il-6, Cxcl10, and Cxcl3 induction, resulting in suppression of subsequent reactive gliosis and demyelination. Our study identifies functional antagonism of S1PR1 as a major mechanism for the protective effect of FTY720 in the cuprizone model and suggests pathogenic contributions of astrocyte S1PR1 signaling in primary demyelination and its potential as a therapeutic target for CNS inflammation.
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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.