Genetics

Metabolites do more than fuel cellular processes; they also regulate immune signaling and neuroinflammation. Three recent studies highlight these mechanisms in multiple sclerosis (MS). Lee et al. demonstrated that astrocyte–CD4⁺ T-cell interactions promote lipid droplet accumulation, supporting NF-κB activation through p65 acetylation and enhancing antigen presentation. Hu et al. identified cGAS–STING activation in reactive astrocytes at chronic active lesion edges, linking extracellular DNA signaling to clusterin-mediated oligodendrocyte apoptosis. Xie et al. identified ARG1-associated metabolic regulation in bone marrow neutrophils, with arginase inhibition reducing disease severity in an experimental model. Together, these findings demonstrate how single-cell and single-nucleus RNA sequencing can identify relevant cell populations and molecular targets, while biochemical and functional experiments establish their mechanistic roles. Targeting metabolic signaling pathways may offer promising therapeutic opportunities in MS, although further clinical validation is needed.