The modulation of S1P receptor signalling and demyelination

Abstract

Sphingosine 1-phosphate receptors are a family of G-protein coupled receptors (GPCRs) that consists of five subtypes (S1PR1-5). These receptors have emerged as therapeutic targets in multiple sclerosis (MS) due to the efficacy of FTY720, also called fingolimod (Gilenya™, Novartis). FTY720 is phosphorylated to its active form (pFTY720) by sphingosine kinases (SphKs) and is an agonist for all S1PRs with the exception of S1PR2. pFTY720 is an immunomodulator that inhibits lymphocyte entry into the periphery and consequent passage into the CNS, thus reducing inflammation and demyelination.