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

Published on: March 5, 2019

PKR, a cognitive decline biomarker, can regulate translation via two consecutive molecular targets p53 and Redd1 in

Milena Damjanac1, Guylène Page1, Stéphanie Ragot2

  • 1Research Group on Brain Aging, University of Poitiers, France.

Journal of Cellular and Molecular Medicine
|February 13, 2009
PubMed

Insights

In Alzheimer's disease, dysregulated protein translation involves increased double-stranded RNA-dependent protein kinase (PKR) and decreased mammalian target of rapamycin (mTOR). This study identifies p53 and Redd1 as downstream targets of PKR, linking PKR to cognitive decline.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Biochemistry

Background:

  • Alzheimer's disease (AD) exhibits dysregulated protein translation, with up-regulated double-stranded RNA-dependent protein kinase (PKR) and down-regulated mammalian target of rapamycin (mTOR).
  • These peripheral alterations in lymphocytes correlate with cognitive and memory deficits in AD patients.
  • The molecular link between PKR and mTOR pathways remains unclear.

Purpose of the Study:

  • To investigate the potential role of tumor suppressor p53 and Redd1 (regulated in development and DNA damage response) as downstream targets of PKR in AD.
  • To analyze the gene and protein levels of p53 and Redd1 in lymphocytes of AD patients compared to controls.
  • To explore correlations between p53, Redd1, active PKR, and cognitive scores (MMSE).

Main Methods:

  • Western blotting and RT-PCR were used to quantify protein and gene expression levels.
  • Lymphocytes from Alzheimer's disease patients and age-matched controls were analyzed.
  • Statistical correlation analyses were performed between molecular markers and Mini Mental State Examination (MMSE) scores.

Main Results:

  • Significant 1.5-fold increase in p53 and Redd1 gene and protein levels in AD lymphocytes.
  • A notable 2.3-fold increase in active p53 protein levels was observed in AD patients.
  • Statistical correlations suggest active PKR phosphorylates p53, leading to Redd1 transcription.

Conclusions:

  • Active PKR, acting via p53 and Redd1, dysregulates translation in AD lymphocytes.
  • PKR levels, but not p53 or Redd1, correlated with cognitive decline (MMSE scores).
  • PKR serves as a potential biomarker for cognitive impairment in Alzheimer's disease.

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