Lysophosphatidic acid receptor 1 influences disease severity in a mouse model of multiple sclerosis
Listed in
This article is not in any list yet, why not save it to one of your lists.Abstract
Multiple sclerosis (MS), a chronic inflammatory disease affecting the central nervous system (CNS), is characterized by demyelination and axonal degeneration. Current treatments, which focus mainly on reducing lymphocyte infiltration into the CNS, are insufficient due to serious side effects and limited effectiveness; thus, identifying drugs with new mechanisms of action is crucial. Lysophosphatidic acid (LPA), a bioactive lipid produced by the enzyme autotaxin, may play a role in MS pathogenesis. Specifically, the LPA 1 subtype of LPA receptors is linked to release of inflammatory cytokines in the CNS, and to demyelination in the peripheral nervous system. Our study investigated the role of LPA 1 in a mouse model of MS. Knocking out the LPA 1 gene in mice with experimental autoimmune encephalomyelitis improved clinical outcomes and reduced demyelination. Additionally, the absence of LPA 1 reduced activation of Iba1-positive cells. Treatment with AM095, an LPA 1 antagonist, tended to improve clinical outcomes and reduce levels of inflammatory mediators. These findings indicate that activation of LPA 1 contributes to MS pathogenesis by promoting microglial activation and infiltration of peripheral immune cells.