PMID- 19210572
OWN - NLM
STAT- MEDLINE
DCOM- 20100719
LR  - 20220716
IS  - 1582-4934 (Electronic)
IS  - 1582-1838 (Print)
IS  - 1582-1838 (Linking)
VI  - 13
IP  - 8B
DP  - 2009 Aug
TI  - PKR, a cognitive decline biomarker, can regulate translation via two consecutive 
      molecular targets p53 and Redd1 in lymphocytes of AD patients.
PG  - 1823-1832
LID - 10.1111/j.1582-4934.2009.00688.x [doi]
AB  - In Alzheimer's disease (AD), the control of translation is dysregulated, 
      precisely, two opposite pathways: double-stranded RNA-dependent protein kinase 
      (PKR) is up-regulated and mammalian target of rapamycin (mTOR) is down-regulated. 
      These biochemical alterations were found at the periphery in lymphocytes of AD 
      patients and were significantly correlated with cognitive and memory test scores. 
      However, the molecular crosslink between these two opposite signalling pathways 
      remains unknown. The tumour suppressor p53 and Redd1 (regulated in development 
      and DNA damage response) could be two downstream targets of active PKR to explain 
      the breakdown of translation in AD patients. In this study, the protein and gene 
      levels of p53 and Redd1 were assayed in lymphocytes of AD patients and in 
      age-matched controls by Western blotting and RT-PCR. Furthermore, correlations 
      were analysed with both the level of active PKR and the Mini Mental State 
      Examination score (MMSE). The results show that the gene and protein levels of 
      p53 and Redd1 were significantly increased about 1.5-fold for both gene and Redd1 
      protein and 2.3-fold for active p53 in AD lymphocytes compared to age-matched 
      controls. Furthermore, statistical correlations between proteins and genes 
      suggest that active PKR could phosphorylate p53 which could induce the 
      transcription of Redd1 gene. No correlations were found between MMSE scores and 
      levels of p53 or Redd1, contrary to active PKR levels. PKR represents a cognitive 
      decline biomarker able to dysregulate translation via two consecutive targets p53 
      and Redd1 in AD lymphocytes.
FAU - Damjanac, Milena
AU  - Damjanac M
AD  - Research Group on Brain Aging, University of Poitiers, France.
FAU - Page, Guylene
AU  - Page G
AD  - Research Group on Brain Aging, University of Poitiers, France.
FAU - Ragot, Stephanie
AU  - Ragot S
AD  - Clinical Investigation Center, Poitiers University Hospital, France.
FAU - Laborie, Guillaume
AU  - Laborie G
AD  - Research Group on Brain Aging, University of Poitiers, France.
FAU - Gil, Roger
AU  - Gil R
AD  - Research Group on Brain Aging, University of Poitiers, France.
AD  - Department of Neurology, Poitiers University Hospital, France.
FAU - Hugon, Jacques
AU  - Hugon J
AD  - Departments of Histology and Pathology, Lariboisiere Hospital, University of 
      Paris, France.
FAU - Paccalin, Marc
AU  - Paccalin M
AD  - Research Group on Brain Aging, University of Poitiers, France.
AD  - Department of Geriatrics, Poitiers University Hospital, France.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090204
PL  - England
TA  - J Cell Mol Med
JT  - Journal of cellular and molecular medicine
JID - 101083777
RN  - 0 (Biomarkers)
RN  - 0 (DDIT4 protein, human)
RN  - 0 (DNA Primers)
RN  - 0 (Transcription Factors)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - EC 2.7.11.1 (eIF-2 Kinase)
SB  - IM
MH  - Aged
MH  - Aged, 80 and over
MH  - Alzheimer Disease/*blood
MH  - Base Sequence
MH  - Biomarkers/*metabolism
MH  - Blotting, Western
MH  - Cognition Disorders/*enzymology
MH  - DNA Primers
MH  - Female
MH  - Humans
MH  - Lymphocytes/*metabolism
MH  - Male
MH  - *Protein Biosynthesis
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Signal Transduction
MH  - Transcription Factors/*blood/genetics
MH  - Tumor Suppressor Protein p53/*blood/genetics
MH  - eIF-2 Kinase/*metabolism
PMC - PMC6529964
EDAT- 2009/02/13 09:00
MHDA- 2010/07/20 06:00
PMCR- 2009/08/01
CRDT- 2009/02/13 09:00
PHST- 2009/02/13 09:00 [entrez]
PHST- 2009/02/13 09:00 [pubmed]
PHST- 2010/07/20 06:00 [medline]
PHST- 2009/08/01 00:00 [pmc-release]
AID - JCMM688 [pii]
AID - 10.1111/j.1582-4934.2009.00688.x [doi]
PST - ppublish
SO  - J Cell Mol Med. 2009 Aug;13(8B):1823-1832. doi: 10.1111/j.1582-4934.2009.00688.x. 
      Epub 2009 Feb 4.