Activation of caspase-11/gasdermin D exacerbates CNS demyelination through a feedforward mechanism
Multiple sclerosis (MS) is a chronic, demyelinating disease of the central nervous system (CNS) characterized by progressive neurological dysfunction. Although caspase-11 and gasdermin D (GSDMD) are known to participate in various inflammatory pathways, their specific roles in demyelinating diseases like MS are not well understood. We investigated the roles of caspase-11 and GSDMD using a cuprizone (CPZ)-induced mouse model of demyelination. Mice were fed a diet containing 0.3% cuprizone for five weeks to induce demyelination. We evaluated the expression of caspase-11 and GSDMD through immunohistochemistry and western blot. Functional impacts were assessed using motor coordination tests and analysis of demyelination and inflammation. RNA sequencing analysis was used to evaluate the effect on the inflammatory environment.