Mechanism of action of s1p receptor modulators in multiple sclerosis: The double requirement

Rev Neurol (Paris). Jan-Feb 2020;176(1-2):100-112. doi: 10.1016/j.neurol.2019.02.007. Epub 2019 Nov 19.

Abstract

The ideal treatment for multiple sclerosis (MS) would target both the neuroinflammatory component of the disease (peripheral and central) and its neurodegenerative component, via modulation of a ubiquitous and pleiotropic common target. Sphingosine-1-phosphate (S1P), a product of sphingosine metabolism, regulates many biological functions (including cell proliferation and survival, cell migration, the immune response and cardiovascular function) via five subtypes of receptor. These receptors are expressed in all types of brain cells where they modulate a number of processes involved in neuronal plasticity, including myelination, neurogenesis and neuroprotection. This profile has aroused interest in modulation of S1P function as a therapeutic target in many brain diseases, particularly those in which the immune system plays a role in the development of brain lesions. Fingolimod, a S1P receptor modulator, exerts its beneficial effects in MS through its anti-inflammatory and anti-neurodegenerative effects. This review discusses recent evidence indicating that fingolimod may target both the inflammatory and neurodegenerative components of the disease process in MS.

Keywords: Fingolimod; Multiple sclerosis; Neurodegeneration; Neuroinflammation; Sphingosine-1-phosphate.

Publication types

  • Review

MeSH terms

  • Animals
  • Brain / drug effects
  • Brain / metabolism
  • Fingolimod Hydrochloride / pharmacology
  • Fingolimod Hydrochloride / therapeutic use
  • Humans
  • Immune System / drug effects
  • Immune System / physiology
  • Immunosuppressive Agents / pharmacology
  • Immunosuppressive Agents / therapeutic use*
  • Lysophospholipids / metabolism
  • Multiple Sclerosis / drug therapy*
  • Multiple Sclerosis / immunology
  • Multiple Sclerosis / metabolism
  • Signal Transduction / drug effects
  • Sphingosine / analogs & derivatives
  • Sphingosine / metabolism
  • Sphingosine-1-Phosphate Receptors / antagonists & inhibitors*
  • Sphingosine-1-Phosphate Receptors / physiology

Substances

  • Immunosuppressive Agents
  • Lysophospholipids
  • Sphingosine-1-Phosphate Receptors
  • sphingosine 1-phosphate
  • Fingolimod Hydrochloride
  • Sphingosine