Glycogen Synthase Kinase Aβ (GSK-3β) is responsible for tau phosphorylation and controls several cellular functions including apoptosis. Another study demonstrated that tunicamycin or Aβ treatment can induce PKR activation in human neuroblastoma cells and can trigger GSK3β activation, as well as tau phosphorylation. They found that in AD brains, both activated PKR and GSK3β co-localize with phosphorylated tau in neurons. In SH-SY5Y cell cultures, tunicamycin and Aβ(1-42) activate PKR, which then can modulate GSK-3β activation and induce tau phosphorylation, apoptosis. All these processes are attenuated by PKR inhibitors or PKR siRNA. PKR could represent a crucial signaling point relaying stress signals to neuronal pathways by interacting with transcription factor or indirectly controlling GSK3β activation, leading to cellular degeneration in AD.