In the context of multiple sclerosis, the presence of TWEAK-expressing macrophages/microglia in cortical lesions and inflamed leptomeninges, along with extensive myelin loss, astrocytosis, neuronal damage, and vascular abnormalities, supports the possibility that TWEAK signaling-mediated macrophages/microglia may have potentially detrimental effects on neural cells expressing the Fn14 (TNFSF12A) receptor [82]. This evidence concerns the gene TNFRSF12A and multiple sclerosis.