PMID- 16098202
OWN - NLM
STAT- MEDLINE
DCOM- 20050930
LR  - 20220225
IS  - 1742-464X (Print)
IS  - 1742-464X (Linking)
VI  - 272
IP  - 16
DP  - 2005 Aug
TI  - Levels of mTOR and its downstream targets 4E-BP1, eEF2, and eEF2 kinase in 
      relationships with tau in Alzheimer's disease brain.
PG  - 4211-20
AB  - The pathogenesis of formation of neurofibrillary tangles (NFTs) in Alzheimer's 
      disease (AD) brains is unknown. One of the possibilities might be that 
      translation of tau mRNA is aberrantly regulated in AD brains. In the current 
      study, levels of various translation control elements including total and 
      phosphorylated (p) forms of mammalian target of rapamycin (mTOR), eukaryotic 
      initiation factor 4E binding protein 1 (4E-BP1), eukaryotic elongation factor 2 
      (eEF2), and eEF2 kinase were investigated in relationship with tau in homogenates 
      of the medial temporal cortex from 20 AD and 10 control brains. We found that 
      levels of p-mTOR (Ser2481), and p-4E-BP1 (Thr70 and Ser65) dramatically increase 
      in AD, and are positively significantly correlated with total tau and p-tau. 
      Levels of p-eEF2K were significantly increased, and total eEF2 significantly 
      decreased in AD, when compared to controls. The changes of p-mTOR (2481), 
      p-4E-BP1, and p-eEF2 were immunohistochemically confirmed to be in neurons of AD 
      brains. This suggested that there are obvious abnormalities of elements related 
      with translation control in AD brain and their aberrant changes may up-regulate 
      the translation of tau mRNA, contributing to hyperphosphorylated tau accumulation 
      in NFT-bearing neurons.
FAU - Li, Xu
AU  - Li X
AD  - Division of Experimental Geriatrics, Department of Neurotec, Karolinska 
      Institutet, Huddinge, Sweden.
FAU - Alafuzoff, Irina
AU  - Alafuzoff I
FAU - Soininen, Hilkka
AU  - Soininen H
FAU - Winblad, Bengt
AU  - Winblad B
FAU - Pei, Jin-Jing
AU  - Pei JJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - FEBS J
JT  - The FEBS journal
JID - 101229646
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Autoantibodies)
RN  - 0 (Carrier Proteins)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (EIF4EBP1 protein, human)
RN  - 0 (Peptide Elongation Factor 2)
RN  - 0 (Phosphoproteins)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.1.17 (EEF2K protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
RN  - EC 2.7.11.20 (Elongation Factor 2 Kinase)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing
MH  - Aged
MH  - Aged, 80 and over
MH  - Alzheimer Disease/enzymology/*metabolism
MH  - Autoantibodies/immunology
MH  - Brain/*metabolism
MH  - Calcium-Calmodulin-Dependent Protein Kinases/*metabolism
MH  - Carrier Proteins/immunology/*metabolism
MH  - Case-Control Studies
MH  - Cell Cycle Proteins
MH  - Elongation Factor 2 Kinase
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Female
MH  - Humans
MH  - Immunohistochemistry
MH  - Male
MH  - Middle Aged
MH  - Peptide Elongation Factor 2/immunology/*metabolism
MH  - Phosphoproteins/immunology/*metabolism
MH  - Phosphorylation
MH  - Protein Kinases/immunology/*metabolism
MH  - TOR Serine-Threonine Kinases
EDAT- 2005/08/16 09:00
MHDA- 2005/10/01 09:00
CRDT- 2005/08/16 09:00
PHST- 2005/08/16 09:00 [pubmed]
PHST- 2005/10/01 09:00 [medline]
PHST- 2005/08/16 09:00 [entrez]
AID - EJB4833 [pii]
AID - 10.1111/j.1742-4658.2005.04833.x [doi]
PST - ppublish
SO  - FEBS J. 2005 Aug;272(16):4211-20. doi: 10.1111/j.1742-4658.2005.04833.x.