Implication of sphingosine-1-phosphate signaling in diseases: molecular mechanism and therapeutic strategies

J Recept Signal Transduct Res. 2017 Oct;37(5):437-446. doi: 10.1080/10799893.2017.1358282. Epub 2017 Jul 31.

Abstract

Sphingosine-1-phosphate signaling is emerging as a critical regulator of cellular processes that is initiated by the intracellular production of bioactive lipid molecule, sphingosine-1-phosphate. Binding of sphingosine-1-phosphate to its extracellular receptors activates diverse downstream signaling that play a critical role in governing physiological processes. Increasing evidence suggests that this signaling pathway often gets impaired during pathophysiological and diseased conditions and hence manipulation of this signaling pathway may be beneficial in providing treatment. In this review, we summarized the recent findings of S1P signaling pathway and the versatile role of the participating candidates in context with several disease conditions. Finally, we discussed its possible role as a novel drug target in different diseases.

Keywords: Sphingosine-1-phosphate receptor; cancer; drug target; microbial diseases; signaling; sphingosine kinase; targeting S1P signaling.

Publication types

  • Review

MeSH terms

  • Arthritis, Rheumatoid / drug therapy
  • Arthritis, Rheumatoid / genetics
  • Ceramidases / genetics
  • Ceramidases / therapeutic use
  • Diabetes Mellitus / drug therapy
  • Diabetes Mellitus / genetics
  • Humans
  • Lysophospholipids / genetics
  • Lysophospholipids / metabolism*
  • Molecular Targeted Therapy*
  • Multiple Sclerosis / drug therapy
  • Multiple Sclerosis / genetics
  • Neoplasms / drug therapy
  • Neoplasms / genetics
  • Phosphotransferases (Alcohol Group Acceptor) / genetics
  • Phosphotransferases (Alcohol Group Acceptor) / therapeutic use
  • Signal Transduction / genetics*
  • Sphingosine / analogs & derivatives*
  • Sphingosine / genetics
  • Sphingosine / metabolism

Substances

  • Lysophospholipids
  • sphingosine 1-phosphate
  • Phosphotransferases (Alcohol Group Acceptor)
  • sphingosine kinase
  • Ceramidases
  • Sphingosine