Ponesimod inhibits astrocyte-mediated neuroinflammation and protects against cingulum demyelination via S1P₁ -selective modulation.

ABSTRACT: Ponesimod is a sphingosine 1-phosphate (S1P) receptor (S1PR) modulator that was recently approved for treating relapsing forms of multiple sclerosis (MS). Three other FDA-approved S1PR modulators for MS-fingolimod, siponimod, and ozanimod-share peripheral immunological effects via common S1P₁ interactions, yet ponesimod may access distinct central nervous system (CNS) mechanisms through its selectivity for the S1P₁ receptor. Here, ponesimod was examined for S1PR internalization and binding, human astrocyte signaling and single-cell RNA-seq (scRNA-seq) gene expression, and in vivo using murine cuprizone-mediated demyelination. Studies confirmed ponesimod's selectivity for S1P₁ without comparable engagement to the other S1PR subtypes (S1P_2,3,4,5 ).

SUBMITTER: Kihara Y 

PROVIDER: S-EPMC8740777 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature