Protein kinase is transcriptionally induced by interferon and activated by double-stranded RNA (dsRNA). PKR inhibits translation initiation through phosphorylation of the ? subunit of the initiation factor eIF2 and also controls the activation of several transcription factors, such as NF-?B, p53, and the Stats. In addition, PKR mediates apoptosis induced by many different stimuli, such as LPS, TNF-?, viral infection, and serum starvation . Activation of PKR by dsRNA results in PKR dimerization and autophosphorylation of Thr446 and Thr451 in the activation loop. Substitution of threonine for alanine at position 451 completely inactivated PKR, while a mutant with a threonine to alanine substitution at position 446 was partially active. Research studies have implicated PKR activation in the pathologies of neurodegenerative diseases, including Alzheimer's disease.