Sphingosine-1-Phosphate: Its Pharmacological Regulation and the Treatment of Multiple Sclerosis: A Review Article
| Autor: | Chiayi Chen, Kyle E Smoot, Elisabeth B Lucassen, Justine Brink, Stanley Cohan |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Ozanimod
business.industry Multiple sclerosis Central nervous system Medicine (miscellaneous) Stimulation Review Pharmacology medicine.disease multiple sclerosis sphingosine-1-phosphate modulators Fingolimod General Biochemistry Genetics and Molecular Biology chemistry.chemical_compound medicine.anatomical_structure chemistry Ponesimod lcsh:Biology (General) medicine Sphingosine-1-phosphate Receptor business lcsh:QH301-705.5 medicine.drug |
| Zdroj: | Biomedicines Biomedicines, Vol 8, Iss 227, p 227 (2020) |
| ISSN: | 2227-9059 |
| Popis: | Sphingosine-1-phosphate (S1P), via its G-protein-coupled receptors, is a signaling molecule with important regulatory properties on numerous, widely varied cell types. Five S1P receptors (S1PR1-5) have been identified, each with effects determined by their unique G-protein-driven downstream pathways. The discovery that lymphocyte egress from peripheral lymphoid organs is promoted by S1P via S1PR-1 stimulation led to the development of pharmacological agents which are S1PR antagonists. These agents promote lymphocyte sequestration and reduce lymphocyte-driven inflammatory damage of the central nervous system (CNS) in animal models, encouraging their examination of efficacy in the treatment of multiple sclerosis (MS). Preclinical research has also demonstrated direct protective effects of S1PR antagonists within the CNS, by modulation of S1PRs, particularly S1PR-1 and S1PR-5, and possibly S1PR-2, independent of effects upon lymphocytes. Three of these agents, fingolimod, siponimod and ozanimod have been approved, and ponesimod has been submitted for regulatory approval. In patients with MS, these agents reduce relapse risk, sustained disability progression, magnetic resonance imaging markers of disease activity, and whole brain and/or cortical and deep gray matter atrophy. Future opportunities in the development of more selective and intracellular S1PR-driven downstream pathway modulators may expand the breadth of agents to treat MS. |
| Databáze: | OpenAIRE |
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