ENDOGENOUS S1P PROTECTS OLIGODENDROCYTE VIABILITY AND IS ESSENTIAL FOR REMYELINATION FOLLOWING A DEMYELINATING INSULT.

• DOI: 10.1016/j.ibneur.2023.08.2061
• Publication Date: 2023-11-05T03:01:27Z
• Authors: Anthony Don; Huitong Song; Jonathan Teo
• Keywords: Remyelination

Therapeutics that promote oligodendrocyte survival and remyelination are needed to restore neurological function in demyelinating diseases such as multiple sclerosis. Sphingosine 1-phosphate (S1P) receptor agonists Fingolimod, Siponimod, Ozanimod, Ponesimod, others clinical immunosuppressants used treat Clinical evidence suggests these drugs also have direct neuroprotective actions the CNS, however experimental support this hypothesis is lacking. S1P an essential lipid metabolite signals through a family of five G-protein coupled receptors. Our recent research demonstrates endogenous S1P, synthesised by enzyme sphingosine kinase 2 (SphK2), important mediator for after treatment with toxin cuprizone. Mice lacking functional SphK2 show loss myelin integrity ageing, further indicative requirement synthesis maintenance. Interestingly, required mature oligodendrocytes, but not progenitor cell proliferation differentiation. Treatment mice 1 5 agonist Siponimod protects against cuprizone-mediated demyelination, reverses effect deficiency on loss. However, does reverse inhibitory remyelination. results therefore indicate both pharmacological activation receptors and/or whereas independent This work establishing protection maintenance functions fundamental understanding potential properties agonists, should guide decision making. None.