Biomolecules & Therapeutics : eISSN 2005-4483 / pISSN 1976-9148

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Fig. 1. Action mechanism of fingolimod and other S1P receptor modulators. Fingolimod is transformed to fingolimod-phosphate in vivo by sphingosine kinases. Fingolimod-phosphate can activate S1P1, S1P3, S1P4, and S1P5, and the fingolimod activation of S1P1 in lymphocytes leads to GRK2-mediated phosphorylation of C-terminal tail of S1P1, which recruits β-arrestin and induces S1P1 internalization. This internalization exposes S1P1 to proteosomal degradation, which prevents the recycling of S1P1 and results in the loss of S1P1 from the plasma membrane. This absence of S1P1 blocks lymphocyte egression from secondary lymphoid organs and reduces T and B cell counts in the blood. Lymphopenia is presumed to be the main mechanism whereby fingolimod causes immune suppression in autoimmune diseases like relapsing multiple sclerosis.
Biomolecules & Therapeutics 2017;25:80~90 https://doi.org/10.4062/biomolther.2016.160
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