FIGURE 2.

NF-κB-signaling in Alzheimer’s and Parkinson’s disease. ADAM17-induced soluble TNFα mediates the activation of the TNF receptor complex, where poly-ubiquitination leads to the recruitment of the LUBAC complex. Linear ubiquitination of NEMO mediates the activation and phosphorylation of the (IκBα) kinase (IKK) complex and consequent activation of NF-κB p50/p65, in turn driving expression of a range of AD-relevant genes such as BIN1, IκBα, APP, BASE1, COX-2, MnSOD, CuZnSOD, or TNFR1. In PD, activation of NF-κB is mediated by PARKIN in a TNFR1-dependent manner.