In contrast, following the failure of global anti-TNFα strategies in HF patients, the development of novel classes of drugs selectively targeting TNFRs, e.g., selective blocking of sTNF/TNFR1 signaling which will preserve functional mTNF/TNFR2 signaling, or combination therapies using sTNF/TNFR1 antagonists together with TNFR2 agonists, might represent a novel superior therapeutic concept to treat a multitude of inflammatory and degenerative diseases including HF [224,225]. This evidence concerns the gene TNFRSF1B and neurodegenerative disease.