Sphingosine-1-phosphate receptor therapies: Advances in clinical trials for CNS-related diseases

Neuropharmacology. 2017 Feb;113(Pt B):597-607. doi: 10.1016/j.neuropharm.2016.11.006. Epub 2016 Nov 4.


The family of sphingosine-1-phosphate receptors (S1PRs) are G protein-coupled and comprise of five subtypes, S1P1-S1P5. These receptors are activated by the sphingolipid ligand, S1P, which is produced from the phosphorylation of sphingosine by sphingosine kinases. The activation of S1PRs modulates a host of cellular processes such as cell proliferation, migration and survival. These receptors are targeted by the drug fingolimod, a first in class oral therapy for multiple sclerosis. Importantly, S1PRs have also been implicated, in cellular experiments, pre-clinical studies and clinical trials in a range of other neurodegenerative diseases, neurological disorders and psychiatric illnesses, where S1PR drugs are proving beneficial. Overall, studies now highlight the importance of S1PRs as targets for modulating a variety of debilitating brain-related diseases. Here, we review the role of S1PRs in these illnesses. This article is part of the Special Issue entitled 'Lipid Sensing G Protein-Coupled Receptors in the CNS'.

Keywords: Ceralifimod (PubChem CID: 11502996); Clinical trials; FTY720; Fingolimod; Fingolimod (PubChem CID: 107970); Ozanimod (PubChem CID: 52938427); Ponesimod (PubChem CID: 11363176); Siponimod (PubChem CID: 44599207); Sphingosine1-phosphate receptors (S1PRs).

Publication types

  • Review

MeSH terms

  • Animals
  • Central Nervous System Agents / pharmacology*
  • Central Nervous System Agents / therapeutic use*
  • Central Nervous System Diseases / drug therapy*
  • Central Nervous System Diseases / metabolism*
  • Clinical Trials as Topic
  • Humans
  • Lysophospholipids / metabolism
  • Receptors, Lysosphingolipid / metabolism*
  • Sphingosine / analogs & derivatives
  • Sphingosine / metabolism


  • Central Nervous System Agents
  • Lysophospholipids
  • Receptors, Lysosphingolipid
  • sphingosine 1-phosphate
  • Sphingosine