PMID- 19631745
OWN - NLM
STAT- MEDLINE
DCOM- 20091207
LR  - 20211203
IS  - 1095-953X (Electronic)
IS  - 0969-9961 (Linking)
VI  - 36
IP  - 1
DP  - 2009 Oct
TI  - Evidence of molecular links between PKR and mTOR signalling pathways in Abeta 
      neurotoxicity: role of p53, Redd1 and TSC2.
PG  - 151-61
LID - 10.1016/j.nbd.2009.07.004 [doi]
AB  - The control of translation is disturbed in Alzheimer's disease (AD). This study 
      analysed the crosslink between the up regulation of double-stranded 
      RNA-dependent-protein kinase (PKR) and the down regulation of mammalian target of 
      rapamycin (mTOR) signalling pathways via p53, the protein Regulated in the 
      Development and DNA damage response 1 (Redd1) and the tuberous sclerosis complex 
      (TSC2) factors in two beta-amyloid peptide (Abeta) neurotoxicity models. In 
      SH-SY5Y cells, Abeta42 induced an increase of P(T451)-PKR and of the ratio 
      p66/(p66+p53) in nuclei and a physical interaction between these proteins. Redd1 
      gene levels increased and P(T1462)-TSC2 decreased. These disturbances were 
      earlier in rat primary neurons with nuclear co-localization of Redd1 and PKR. The 
      PKR gene silencing in SH-SY5Y cells prevented these alterations. p53, Redd1 and 
      TSC2 could represent the molecular links between PKR and mTOR in Abeta 
      neurotoxicity. PKR could be a critical target in a therapeutic program of AD.
FAU - Morel, Milena
AU  - Morel M
AD  - Research Group on Brain Aging, GReViC EA 3808, University of Poitiers, 6 rue de 
      la Miletrie BP 199, 86034 Poitiers Cedex, France.
FAU - Couturier, Julien
AU  - Couturier J
FAU - Pontcharraud, Raymond
AU  - Pontcharraud R
FAU - Gil, Roger
AU  - Gil R
FAU - Fauconneau, Bernard
AU  - Fauconneau B
FAU - Paccalin, Marc
AU  - Paccalin M
FAU - Page, Guylene
AU  - Page G
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090723
PL  - United States
TA  - Neurobiol Dis
JT  - Neurobiology of disease
JID - 9500169
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Ddit4 protein, rat)
RN  - 0 (Peptide Fragments)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Repressor Proteins)
RN  - 0 (TSC2 protein, human)
RN  - 0 (Transcription Factors)
RN  - 0 (Tsc2 protein, rat)
RN  - 0 (Tuberous Sclerosis Complex 2 Protein)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - 0 (Tumor Suppressor Proteins)
RN  - 0 (amyloid beta-protein (1-42))
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.1.1 (mTOR protein, rat)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (eIF-2 Kinase)
SB  - IM
MH  - Amyloid beta-Peptides/*toxicity
MH  - Analysis of Variance
MH  - Animals
MH  - Cell Nucleus/drug effects/metabolism
MH  - Cells, Cultured
MH  - Cerebral Cortex/cytology
MH  - Cytoplasm/drug effects/metabolism
MH  - Embryo, Mammalian
MH  - Gene Expression Regulation/drug effects/genetics
MH  - Humans
MH  - Immunoprecipitation/methods
MH  - Neuroblastoma/pathology
MH  - Neurons/cytology/*drug effects
MH  - Peptide Fragments/*toxicity
MH  - Phosphorylation/drug effects
MH  - Protein Kinases/genetics/*metabolism
MH  - RNA, Small Interfering/genetics/metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Repressor Proteins/genetics/metabolism
MH  - Signal Transduction/*drug effects
MH  - TOR Serine-Threonine Kinases
MH  - Transcription Factors
MH  - Transfection/methods
MH  - Tuberous Sclerosis Complex 2 Protein
MH  - Tumor Suppressor Protein p53/metabolism
MH  - Tumor Suppressor Proteins/genetics/*metabolism
MH  - eIF-2 Kinase/genetics/*metabolism
EDAT- 2009/07/28 09:00
MHDA- 2009/12/16 06:00
CRDT- 2009/07/28 09:00
PHST- 2009/04/21 00:00 [received]
PHST- 2009/07/03 00:00 [revised]
PHST- 2009/07/13 00:00 [accepted]
PHST- 2009/07/28 09:00 [entrez]
PHST- 2009/07/28 09:00 [pubmed]
PHST- 2009/12/16 06:00 [medline]
AID - S0969-9961(09)00177-6 [pii]
AID - 10.1016/j.nbd.2009.07.004 [doi]
PST - ppublish
SO  - Neurobiol Dis. 2009 Oct;36(1):151-61. doi: 10.1016/j.nbd.2009.07.004. Epub 2009 
      Jul 23.