title: The neurobiology of sphingosine 1-phosphate signaling and sphingosine 1-phosphate receptor modulators.
abstract: Sphingosine 1-phosphate receptors (S1PRs) are G protein-coupled receptors expressed by many cell types, including immune and neural cells. These receptors are promising targets for immunomodulatory and possibly neuromodulatory therapies. Fingolimod (FTY720) is a sphingosine analog that, when phosphorylated, becomes a prototypical S1PR modulator. It has recently been approved as the first oral treatment for relapsing forms of multiple sclerosis in some countries. Fingolimod has documented effects on lymphocyte egress, selectively retaining lymphocytes within the lymph nodes. In addition, fingolimod can enter the CNS and can act on S1PRs expressed by most neural lineages. In this article, we discuss recent results supporting the concept that S1PR modulators may exert neuroprotective and regenerative actions in the CNS as well as having anti-inflammatory effects.
authors.affiliation: Department of Neurology, University of Chicago, IL 60637, USA. bsoliven@neurology.bsd.uchicago.edu
authors.forename: Betty
authors.initials: B
authors.lastname: Soliven
authors.forename: Veronique
authors.initials: V
authors.lastname: Miron
authors.forename: Jerold
authors.initials: J
authors.lastname: Chun
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000502:physiology; D002490:Central Nervous System / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000068876:Fingolimod Hydrochloride; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use; D008214:Lymphocytes / Q000187:drug effects; D008246:Lysophospholipids / Q000378:metabolism*; D009446:Neurobiology; D009457:Neuroglia / Q000187:drug effects; D009474:Neurons / Q000187:drug effects; D011409:Propylene Glycols / Q000494:pharmacology / Q000627:therapeutic use; D049349:Receptors, Lysosphingolipid / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D007155:Immunologic Factors; D007166:Immunosuppressive Agents; D008246:Lysophospholipids; D011409:Propylene Glycols; D049349:Receptors, Lysosphingolipid; C060506:sphingosine 1-phosphate; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine