However, anti–TNF-α therapies have largely failed in the treatment of neurodegenerative diseases, probably due to the antithetic functions of the two TNF receptors, with TNFR1 being responsible for proinflammatory and proapoptotic signaling, whereas TNFR2 signaling induces immunomodulatory and regenerative processes. This evidence concerns the gene TNFRSF1B and neurodegenerative disease.