Modulation of tau phosphorylation by the kinase PKR: implications in Alzheimer's disease.
Article Details
- CitationCopy to clipboard
Bose A, Mouton-Liger F, Paquet C, Mazot P, Vigny M, Gray F, Hugon J
Modulation of tau phosphorylation by the kinase PKR: implications in Alzheimer's disease.
Brain Pathol. 2011 Mar;21(2):189-200. doi: 10.1111/j.1750-3639.2010.00437.x. Epub 2010 Oct 3.
- PubMed ID
- 21029237 [ View in PubMed]
- Abstract
Double-stranded RNA dependent kinase (PKR) is a pro-apoptotic kinase that controls protein translation. Previous studies revealed that activated PKR is increased in brains with Alzheimer's disease (AD). Glycogen Synthase Kinase Abeta (GSK-3beta) is responsible for tau phosphorylation and controls several cellular functions also including apoptosis. The goal of this work was to determine if PKR could concurrently trigger GSK-3beta activation, tau phosphorylation and apoptosis. In AD brains, both activated kinases co-localize with phosphorylated tau in neurons. In SH-SY5Y cell cultures, tunicamycin and Abeta(1-42) activate PKR, GSK-3beta and induce tau phosphorylation and all these processes are attenuated by PKR inhibitors or PKR siRNA. Our results demonstrate that neuronal PKR co-localizes with GSK-3beta and tau in AD brains and is able to modulate GSK-3beta activation, tau phosphorylation and apoptosis in neuroblastoma cells exposed to tunicamycin or Abeta. PKR could represent a crucial signaling point relaying stress signals to neuronal pathways leading to cellular degeneration in AD.