IRS1 and Alzheimer disease: Studies performed in human and mouse models of AD highlighted the role of inflammation and in particular the inflammatory cytokine tumor necrosis factor alpha (TNF-α), which leads to the activation of specific kinases [i.e., Jun N-terminal kinase (JNK), I kappa B kinase (IKK), and protein kinase R (PKR)] (Bomfim et al., 2012; Lourenco et al., 2013) and endoplasmic reticulum (ER) stress (PKR-mediated phosphorylation of eIF2α) (Lourenco et al., 2013) responsible for IRS1 inhibition (Figure 2).