PKR is an interferon-inducible serine/threonine specific protein kinase. It is widely expressed in eukaryotic organisms and activated by double stranded RNA. Activation of PKR by dsRNAs leads to autophosphorylation at multiple sites. Phosphorylation of Thr446 and Thr451 in the PKR activation loop is required in vivo and in vitro for high level kinase activity. PKR phosphorylates its natural substrate, the alpha subunit of eukaryotic protein synthesis initiation factor 2 (EIF2 alpha), leading to the inhibition of protein synthesis. PKR is also involved in TLR signaling and mediates apoptosis in fibroblasts in response to viral infection and inflammatory cytokines, and also activates IKK and NFKB, thereby suppressing apoptosis. Recently, it has been reported that PKR also phosphorylates human p53 on serine 392. PKR might play a role in ER stress-induced apoptosis and in Alzheimer's disease. Alzheimer cases show prominent PKR activation in association with neuritic plaques and pyramidal neurons in the hippocampus and neocortex.