Open AccessModulation of Tau Phosphorylation by the Kinase PKR: Implications in Alzheimer's Disease
Author(s) -
Bose Anindita,
MoutonLiger François,
Paquet Claire,
Mazot Pierre,
Vigny Marc,
Gray Françoise,
Hugon Jacques
Publication year - 2011
Publication title -
brain pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.986
H-Index - 132
eISSN - 1750-3639
pISSN - 1015-6305
DOI - 10.1111/j.1750-3639.2010.00437.x
Subject(s) - protein kinase r , phosphorylation , gsk 3 , microbiology and biotechnology , eif 2 kinase , kinase , tunicamycin , protein kinase a , biology , signal transduction , ask1 , sh sy5y , chemistry , mitogen activated protein kinase kinase , cyclin dependent kinase 2 , unfolded protein response , neuroblastoma , cell culture , endoplasmic reticulum , genetics
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 Aβ (GSK‐3β) 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‐3β 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 Aβ 1‐42 activate PKR, GSK‐3β 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‐3β and tau in AD brains and is able to modulate GSK‐3β activation, tau phosphorylation and apoptosis in neuroblastoma cells exposed to tunicamycin or Aβ. PKR could represent a crucial signaling point relaying stress signals to neuronal pathways leading to cellular degeneration in AD.