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Lessons from S1P receptor targeting in multiple sclerosis.

Emanuela Colombo1, Cinthia Farina1

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Pharmacology & Therapeutics
|August 27, 2021
PubMed
Summary

Sphingosine 1-phosphate (S1P) receptor modulators, used for multiple sclerosis, impact immune cells and may affect the central nervous system. This review explores S1P signaling in neuroimmunology for broader therapeutic applications.

Keywords:
FingolimodMultiple sclerosisNeuroinflammationSphingosine-1-phosphateSphingosine-1-phosphate modulators

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Area of Science:

  • Neuroimmunology
  • Pharmacology
  • Cellular Signaling

Background:

  • Sphingosine 1-phosphate (S1P) is a bioactive lipid crucial for immune and nervous system functions.
  • The S1P-S1P receptor axis is implicated in neuroinflammatory and autoimmune diseases.
  • Approved S1P receptor modulators primarily treat multiple sclerosis by inhibiting lymphocyte trafficking.

Purpose of the Study:

  • To review the role of S1P signaling in neuroimmunology.
  • To integrate evidence from S1P modulator mechanisms in multiple sclerosis with findings from animal models and in vitro studies.
  • To explore potential therapeutic applications of S1P receptor targeting beyond current indications.

Main Methods:

  • Literature review integrating data on S1P receptor modulator mechanisms.
  • Analysis of evidence from neuroinflammatory animal models.
  • Inclusion of in vitro observations on S1P signaling.

Main Results:

  • S1P modulators induce lymphopenia by disrupting lymphocyte egress.
  • Emerging evidence suggests S1P modulators have immunological effects beyond lymphocyte trafficking.
  • These drugs can cross the blood-brain barrier and target central nervous system resident cells.

Conclusions:

  • S1P signaling plays a significant role in neuroimmunology.
  • Understanding S1P modulator mechanisms offers insights into treating neuroinflammatory conditions.
  • Targeting S1P receptors holds promise for treating a wider range of diseases.