Sphingosine-1-phosphate receptor modulators in stroke treatment

J Neurochem. 2022 Sep;162(5):390-403. doi: 10.1111/jnc.15685. Epub 2022 Aug 16.

Abstract

Sphingosine-1-phosphate (S1P) is a bioactive lysophospholipid that can influence a broad range of biological processes through its binding to five distinct G-protein-coupled receptors. S1P receptor modulators are a new group of immunosuppressive agents currently used in the immunotherapy of multiple sclerosis. Inflammation following stroke can exacerbate neuronal injury. Given that S1P signaling is linked to multiple immune processes, therapies targeting the S1P axis may be suitable for treating stroke. In this review, we outline S1P metabolism and S1P receptors, discuss the mechanisms of action of S1P receptor modulators in lymphocyte migration and their direct action on cells of the central nervous system, and provide a concise summary of the efficacy of S1P receptor modulators in animal studies and clinical trials on treatments for stroke.

Keywords: fingolimod; inflammation; sphingosine-1-phosphate receptor modulators; stroke.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Fingolimod Hydrochloride / pharmacology
  • Immunosuppressive Agents / pharmacology
  • Lysophospholipids / metabolism
  • Multiple Sclerosis* / metabolism
  • Receptors, Lysosphingolipid / metabolism
  • Sphingosine 1 Phosphate Receptor Modulators*
  • Sphingosine-1-Phosphate Receptors
  • Stroke* / drug therapy

Substances

  • Immunosuppressive Agents
  • Lysophospholipids
  • Receptors, Lysosphingolipid
  • Sphingosine 1 Phosphate Receptor Modulators
  • Sphingosine-1-Phosphate Receptors
  • Fingolimod Hydrochloride