TNF and obesity due to melanocortin 4 receptor deficiency: In ageing, as well as in AD, diabetes and obesity, all three UPR signalling pathways trigger and sustain the production of microglial and astrocytes pro-inflammatory NO (eliciting nitrative stress protein modification) and cytokines (e.g., TNFα, IL1β) through the NFκB pathway, and NFκB activated iNOS.