Tumor necrosis factor (TNF) has been implicated in the pathogenesis of several neurological disorders, such as multiple sclerosis (MS). Its transmembrane form activates the type II tumor necrosis factor receptor (TNFR2), functioning via cell-to-cell contact. In contrast, its soluble form activates TNFR1; studies in animal models have evidenced TNFR1 to activate neurotoxic pathways, while TNFR2 activation pathways may have protective effects within the central nervous system due to activation of reparative mechanisms.