ArticleThe American journal of pathology2008
Cyclical and dose-dependent responses of adult human mature oligodendrocytes to fingolimod.
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. Cited by 36 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 93 citations in OpenAlex.
- Effects of Sphingosine 1-phosphate Modulators on Central Remyelination: A Systematic Review of Animal Models.Cellular and molecular neurobiology · 2026Pooled it
- Effects of sphingosine-1-phosphate receptor modulators on remyelination in multiple sclerosis: evidence fromFrontiers in immunology · 2026Review
- Design and Synthesis of Novel PET Radiotracers for Imaging Sphingosine-1-Phosphate Receptor 5 (S1PR5) in the Brain.Journal of medicinal chemistry · 2025Article
- Molecular and neuroimmune pharmacology of S1P receptor modulators and other disease-modifying therapies for multiple sclerosis.Pharmacology & therapeutics · 2023Review
- 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
- The emerging role of FTY720 as a sphingosine 1-phosphate analog for the treatment of ischemic stroke: The cellular and molecular mechanisms.Brain and behavior · 2021Review
- Novel Potent Selective Orally Active S1P5 Receptor Antagonists.ACS medicinal chemistry letters · 2021Article
- AFrontiers in neuroscience · 2021Review
- Sphingosine-1-Phosphate Receptor Modulators and Oligodendroglial Cells: Beyond Immunomodulation.International journal of molecular sciences · 2020Review
- Long noncoding RNAs APOA1-AS, IFNG-AS1, RMRP and their related biomolecules in Egyptian patients with relapsing-remitting multiple sclerosis: Relation to disease activity and patient disability.Journal of advanced research · 2020Article
- Effect of Fingolimod on Neural Stem Cells: A Novel Mechanism and Broadened Application for Neural Repair.Molecular therapy : the journal of the American Society of Gene Therapy · 2017Article
- The Direct Effects of Fingolimod in the Central Nervous System: Implications for Relapsing Multiple Sclerosis.CNS drugs · 2016Review
- Sphingosine-1-phosphate receptor antagonism enhances proliferation and migration of engrafted neural progenitor cells in a model of viral-induced demyelination.The American journal of pathology · 2015Article
- Fingolimod prevents blood-brain barrier disruption induced by the sera from patients with multiple sclerosis.PloS one · 2015Article
- The sphingosine 1-phosphate receptor agonist FTY720 is neuroprotective after cuprizone-induced CNS demyelination.British journal of pharmacology · 2015Article
- Heterogeneity of oligodendrocyte progenitor cells in adult human brain.Annals of clinical and translational neurology · 2014Article
- Fingolimod for the treatment of neurological diseases-state of play and future perspectives.Frontiers in cellular neuroscience · 2014Review
- Molecular pharmacodynamics of new oral drugs used in the treatment of multiple sclerosis.Drug design, development and therapy · 2014Review
- Article
- Diffusion tensor imaging detects treatment effects of FTY720 in experimental autoimmune encephalomyelitis mice.NMR in biomedicine · 2013Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 3 countries.
Funding
Abstract
Fingolimod is a sphingosine-1-phosphate (S1P) analogue that has been used in clinical trials as a systemic immunomodulatory therapy for multiple sclerosis. Fingolimod readily accesses the central nervous system, raising the issue of its direct effects on neural cells. We assessed the effects of active fingolimod on dissociated cultures of mature, myelin-producing oligodendrocytes (OLGs) derived from adult human brain. Human OLGs express S1P receptor transcripts in relative abundance of S1P5>S1P3>S1P1, with undetectable levels of S1P4. Low doses of fingolimod (100 pmol/L to 1 nmol/L) induced initial membrane elaboration (2 days), subsequent retraction (4 days), and recurrence of extension with prolonged treatment (8 days). Higher doses (10 nmol/L to 1 mumol/L) caused the opposite modulation of membrane dynamics. Retraction was rescued by co-treatment with the S1P3/S1P5 pathway antagonist, suramin, and was associated with RhoA-mediated cytoskeletal signaling. Membrane elaboration was mimicked using the S1P1 agonist SEW2871. Fingolimod rescued human OLGs from serum and glucose deprivation-induced apoptosis, which was reversed with suramin co-treatment and mimicked using an S1P5 agonist. High doses of fingolimod induced an initial down-regulation of S1P5 mRNA levels relative to control (4 hours), subsequent up-regulation (2 days), and recurrent down-regulation (8 days). S1P1 mRNA levels were inversely regulated compared with S1P5. These results indicate that fingolimod modulates maturity- and species-specific OLG membrane dynamics and survival responses that are directly relevant for myelin integrity.
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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.