ArticleProceedings of the National Academy of Sciences of the United States of America2022
Siponimod ameliorates metabolic oligodendrocyte injury via the sphingosine-1 phosphate receptor 5.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 21 citations in OpenAlex.
- Effects of Sphingosine 1-phosphate Modulators on Central Remyelination: A Systematic Review of Animal Models.Cellular and molecular neurobiology · 2026Pooled it
- Fingolimod Alleviates Neuroinflammation and Blood-Brain Barrier Disruption in Epilepsy by Upregulating S1PR5 and Inhibiting the Rho/ROCK/NF-κB Pathway.CNS neuroscience & therapeutics · 2026Article
- Review
- CD44 as a Conserved Biomarker and Functional Modulator of Neuroinflammation in Multiple Sclerosis and Beyond.Molecular neurobiology · 2026Article
- Article
- Loss of oligodendrocyte transcription factor 2 protein expression in metabolically stressed oligodendrocytes.Acta neuropathologica · 2026Article
- Unraveling multiple sclerosis: a hidden interaction between intestinal microbiota and host lipid metabolism.Gut microbes · 2025Review
- How do different cell populations orchestrate myelin regeneration?Biochemical Society transactions · 2025Review
- Siponimod supports remyelination in the non-supportive environment.Scientific reports · 2025Article
- Deciphering the role of sphingosine 1-phosphate in central nervous system myelination and repair.Journal of neurochemistry · 2025Review
- Remyelination in the Central Nervous System.Cold Spring Harbor perspectives in biology · 2024Review
- How to Use the Cuprizone Model to Study De- and Remyelination.International journal of molecular sciences · 2024Review
- Astrocytes: Lessons Learned from the Cuprizone Model.International journal of molecular sciences · 2023Review
- Article
- Molecular and neuroimmune pharmacology of S1P receptor modulators and other disease-modifying therapies for multiple sclerosis.Pharmacology & therapeutics · 2023Review
- FirstTheranostics · 2023Article
- Remyelination in Multiple Sclerosis: Findings in the Cuprizone Model.International journal of molecular sciences · 2022Review
- 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
- Systemic immune derangements are shared across various CNS pathologies and reflect novel mechanisms of immune privilege.Neuro-oncology advancesReview
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Multiple sclerosis (MS), an autoimmune-driven, inflammatory demyelinating disease of the central nervous system (CNS), causes irreversible accumulation of neurological deficits to a variable extent. Although there are potent disease-modifying agents for its initial relapsing-remitting phase, immunosuppressive therapies show limited efficacy in secondary progressive MS (SPMS). Although modulation of sphingosine-1 phosphate receptors has proven beneficial during SPMS, the underlying mechanisms are poorly understood. In this project, we followed the hypothesis that siponimod, a sphingosine-1 phosphate receptor modulator, exerts protective effects by direct modulation of glia cell function (i.e., either astrocytes, microglia, or oligodendrocytes). To this end, we used the toxin-mediated, nonautoimmune MS animal model of cuprizone (Cup) intoxication. On the histological level, siponimod ameliorated cuprizone-induced oligodendrocyte degeneration, demyelination, and axonal injury. Protective effects were evident as well using GE180 translocator protein 18-kDa (TSPO) imaging with positron emission tomography (PET)/computed tomography (CT) imaging or next generation sequencing (NGS). Siponimod also ameliorated the cuprizone-induced pathologies in
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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.