FTY720 in CNS injuries: Molecular mechanisms and therapeutic potential

Brain Res Bull. 2020 Nov:164:75-82. doi: 10.1016/j.brainresbull.2020.08.013. Epub 2020 Aug 23.

Abstract

Central nervous system (CNS) injuries, such as traumatic brain injury (TBI), subarachnoid hemorrhage (SAH) and intracerebral hemorrhage (ICH), are important causes of disability and death worldwide. FTY720, a structural sphingosine analog and sphingosine-1-phosphate receptor (S1PR) modulator, is currently used in the treatment of relapsing-remitting multiple sclerosis (RRMS). However, recent in vivo and in vitro studies suggest that FTY720 plays a key role in many neurological diseases, especially in CNS injuries. In addition, FTY720 is under clinical trial for the treatment of acute stroke and ICH. FTY720 could exert anti-apoptosis, anti-inflammation and anti-oxidative stress effects in CNS injuries through different molecules and pathways such as sphingosine-1-phosphate receptor (S1PR), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), phosphatidylinositol-4,5-bisphosphate 3-kinase/protein kinase B (PI3K/AKT), protein phosphatase 2A (PP2A) and P2 × 7 receptor (P2 × 7R). Thus, FTY720 shows great promise for the treatment of CNS injuries. This review covers a brief introduction about the relationship between FTY270 and CNS injuries, and an updated overview of downstream molecules of FTY720 in CNS injuries.

Keywords: Apoptosis; Autophagy; Central nervous system injuries; Downstream molecules; FTY720; Oxidative stress.

Publication types

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

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Autophagy / drug effects*
  • Brain Injuries / drug therapy*
  • Brain Injuries / metabolism
  • Fingolimod Hydrochloride / pharmacology
  • Fingolimod Hydrochloride / therapeutic use*
  • Neuroprotective Agents / pharmacology*
  • Neuroprotective Agents / therapeutic use
  • Oxidative Stress / drug effects*
  • Spinal Cord Injuries / drug therapy*
  • Spinal Cord Injuries / metabolism

Substances

  • Neuroprotective Agents
  • Fingolimod Hydrochloride