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Studying RNA Interactors of Protein Kinase RNA-Activated during the Mammalian Cell Cycle
10:05

Studying RNA Interactors of Protein Kinase RNA-Activated during the Mammalian Cell Cycle

Published on: March 5, 2019

PKR, the double stranded RNA-dependent protein kinase as a critical target in Alzheimer's disease

Milena Morel1, Julien Couturier, Claire Lafay-Chebassier

  • 1Research Group on Brain Aging (EA 3808) University of Poitiers, Poitiers Cedex, France.

Journal of Cellular and Molecular Medicine
|July 16, 2009
PubMed

Insights

Alzheimer's disease (AD) involves amyloid beta-peptide deposits and neurofibrillary tangles. Increased PKR signaling in AD patients correlates with cognitive decline, suggesting PKR as an early biomarker and therapeutic target.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Biochemistry

Background:

  • Alzheimer's disease (AD) is characterized by amyloid beta-peptide (Abeta) deposits and neurofibrillary tangles, leading to neuronal death.
  • Dysregulation of protein translation, controlled by eukaryotic initiation factors (eIF2 and eIF4E), is implicated in AD pathogenesis.
  • The double-stranded RNA-dependent protein kinase (PKR) pathway, which inhibits protein synthesis, is upregulated in AD, while the mammalian target of rapamycin (mTOR) pathway, promoting translation, is downregulated.

Purpose of the Study:

  • To investigate the role of PKR and mTOR signaling pathways in Alzheimer's disease.
  • To determine if PKR and eIF2alpha modifications in lymphocytes correlate with cognitive function in AD patients.
  • To explore potential molecular links between PKR and mTOR pathways, such as p53 and tuberous sclerosis complex 2.

Main Methods:

  • Analysis of phosphorylated PKR and eIF2alpha levels in lymphocytes from AD patients.
  • Correlation analysis between PKR/eIF2alpha levels and cognitive/memory test scores.
  • Review of existing literature on PKR and mTOR signaling in AD models and patients.

Main Results:

  • Phosphorylated PKR and eIF2alpha levels were significantly elevated in lymphocytes of AD patients.
  • These elevated levels showed a significant correlation with cognitive and memory test performance.
  • PKR signaling is upregulated, while mTOR signaling is downregulated in AD, with potential links via p53 and TSC2.

Conclusions:

  • PKR activation and subsequent protein synthesis inhibition may contribute to neuronal dysfunction in AD.
  • Elevated PKR and eIF2alpha in peripheral cells could serve as early biomarkers for AD.
  • Targeting the PKR pathway presents a potential therapeutic strategy for Alzheimer's disease.

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