Siponimod Modulates the Reaction of Microglial Cells to Pro-Inflammatory Stimulation.
Joel GruchotFerdinand LeinIsabel LewenLaura ReicheVivien WeyersPatrick PetzschPeter GöttleKarl KöhrerHans-Peter HartungPatrick KüryDavid KremerPublished in: International journal of molecular sciences (2022)
Siponimod (Mayzent ® ), a sphingosine 1-phosphate receptor (S1PR) modulator which prevents lymphocyte egress from lymphoid tissues, is approved for the treatment of relapsing-remitting and active secondary progressive multiple sclerosis. It can cross the blood-brain barrier (BBB) and selectively binds to S1PR1 and S1PR5 expressed by several cell populations of the central nervous system (CNS) including microglia. In multiple sclerosis, microglia are a key CNS cell population moving back and forth in a continuum of beneficial and deleterious states. On the one hand, they can contribute to neurorepair by clearing myelin debris, which is a prerequisite for remyelination and neuroprotection. On the other hand, they also participate in autoimmune inflammation and axonal degeneration by producing pro-inflammatory cytokines and molecules. In this study, we demonstrate that siponimod can modulate the microglial reaction to lipopolysaccharide-induced pro-inflammatory activation.
Keyphrases
- multiple sclerosis
- lipopolysaccharide induced
- inflammatory response
- white matter
- blood brain barrier
- neuropathic pain
- lps induced
- single cell
- cell therapy
- induced apoptosis
- spinal cord injury
- gene expression
- cell cycle arrest
- mesenchymal stem cells
- systemic lupus erythematosus
- endoplasmic reticulum stress
- cell proliferation
- binding protein
- electron transfer
- optical coherence tomography
- smoking cessation
- drug administration
- optic nerve