TNFR2 – Target for Therapeutics Against Neurodegenerative Diseases?

Tumor necrosis factor α (TNFα) is a proinflammatory cytokine which acts via its two receptors TNFR1 and TNFR2. It is involved in many cell types in various cellular functions of cell growth, differentiation, and cellular apoptosis. Whereas soluble TNF has the highest affinity for TNFR1 and is therefore its main activator, the membrane standing precursor form of TNF was found to be the strongest activator of TNFR2. This may be also the simple technical reason why for a very long time hardly any TNFR2-specific response was known. In fact for a very long time TNFR2 was believed to function as ligand-passing receptor to TNFR1 or to be just a costimulator of TNFR1 signaling events. In fact under certain conditions this might be true yet a specific and TNFR1-independent signaling role was until recently not established [24].