As an insulin receptor substrate 1 (IRS-1)-inactivating serine kinase, JNK, in cooperation with the inflammation/PICR-induced serine kinases inhibitor of κB–kinase β (IKKβ) and protein kinase R (PKR), also induces neuronal insulin resistance to exacerbate the production, accumulation and aggregation of Aβ (see Figure 1 and details in section “Insulin resistance and the neuronal energy metabolism”) as well as Tau hyperphosphorylation (section “GLP-1R mimetics suppress Tau hyperphosphorylation and aggregation during AD”). Here, IRS1 is linked to Alzheimer disease.