Modulation of Tau Phosphorylation by the Kinase PKR: Implications in Alzheimer's Disease
説明
<jats:title>Abstract</jats:title><jats:p>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<jats:sub>1‐42</jats:sub> 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.</jats:p>
収録刊行物
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- Brain Pathology
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Brain Pathology 21 (2), 189-200, 2010-10-03
Wiley
