ponesimod and Alzheimer-Disease

Previously, we showed that the sphingosine-1-phosphate (S1P) transporter spinster 2 (Spns2) mediates activation of microglia in response to amyloid β peptide (Aβ). Here, we investigated if Ponesimod, a functional S1P receptor 1 (S1PR1) antagonist, prevents Aβ-induced activation of glial cells and Alzheimer's disease (AD) pathology.. We used primary cultures of glial cells and the 5XFAD mouse model to determine the effect of Aβ and Ponesimod on glial activation, Aβ phagocytosis, cytokine levels and pro-inflammatory signaling pathways, AD pathology, and cognitive performance.. Aβ. Ponesimod targeting S1PR1 is a promising therapeutic approach to reprogram microglia, reduce neuroinflammation, and increase Aβ clearance in AD.. NIHR01AG064234, RF1AG078338, R21AG078601, VAI01BX003643.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Anti-Inflammatory Agents; Cytokines; Disease Models, Animal; Mice; Mice, Transgenic; Microglia; Neuroinflammatory Diseases; Sphingosine-1-Phosphate Receptors; Toll-Like Receptor 4