title: Central effects of fingolimod.
abstract: BACKGROUND
  Fingolimod, a sphingosine-1-phosphate receptor modulator, was the first oral therapy approved for relapsing-remitting multiple sclerosis, and shows a novel mechanism of action. Upon binding to S1P1 receptors in lymphocytes, the selective retention of naive and central memory T cells in secondary lymphoid tissues is promoted, preventing their egress to the central nervous system (CNS). In addition, fingolimod readily crosses the blood brain barrier, and several reports suggest a direct neuroprotective effect in the CNS.
  
  
  OBJECTIVE
  To review the available data on the central effects of fingolimod.
  
  
  METHODS
  Imbalances between damage and repair processes are a reflection of chronic demyelination, axonal degeneration and gliosis, and seem to contribute to multiple sclerosis associated disability. Given fingolimod readily crosses the blood brain barrier, it can exert its action directly on S1P receptors present in CNS cells. Fingolimod occupies S1P receptors in oligodendrocytes, oligodendrocyte precursor cells, astrocytes, microglial cells and neurons, promoting remyelination, neuroprotection, and endogenous regeneration processes. Efficacy results from clinical trials are consistent with a mechanism of action that includes direct effects in CNS cells.
  
  
  CONCLUSIONS
  Current evidence suggests that the efficacy of fingolimod in the treatment of Multiple Sclerosis is due to its dual action as an immunomodulatory molecule and as a direct modulator of S1PRs in the CNS. In fact, recent reports propose that fingolimod has neuroprotective effects in several models, and open new avenues of potential therapeutic applications, such as Alzheimer's disease, cerebral malaria, neuroblastoma and neuroprotection in cranial irradiation.
authors.affiliation: Centro Hospitalar de Entre o Douro e Vouga, E.P.E, Santa Maria da Feira, Portugal.
authors.forename: Vítor T
authors.initials: VT
authors.lastname: Cruz
authors.forename: Joaquim
authors.initials: J
authors.lastname: Fonseca
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D002986:Clinical Trials as Topic; D004195:Disease Models, Animal; D000068876:Fingolimod Hydrochloride; D006801:Humans; D007156:Immunologic Memory; D051379:Mice; D018345:Mice, Knockout; D008818:Mice, Neurologic Mutants; D015337:Multicenter Studies as Topic; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy; D055495:Neurogenesis / Q000187:drug effects; D009457:Neuroglia / Q000187:drug effects; D018696:Neuroprotective Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D011409:Propylene Glycols / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D049349:Receptors, Lysosphingolipid / Q000187:drug effects; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology
chemical_list: D018696:Neuroprotective Agents; D011409:Propylene Glycols; D049349:Receptors, Lysosphingolipid; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine