PMID- 19301428
OWN - NLM
STAT- MEDLINE
DCOM- 20090831
LR  - 20211203
IS  - 1097-4547 (Electronic)
IS  - 0360-4012 (Linking)
VI  - 87
IP  - 10
DP  - 2009 Aug 1
TI  - Amyloid-beta interrupts the PI3K-Akt-mTOR signaling pathway that could be 
      involved in brain-derived neurotrophic factor-induced Arc expression in rat 
      cortical neurons.
PG  - 2297-307
LID - 10.1002/jnr.22057 [doi]
AB  - The deposition of amyloid-beta (Abeta) contributes to the pathogenesis of 
      Alzheimer's disease. Even at low levels, Abeta may interfere with various 
      signaling cascades critical for the synaptic plasticity that underlies learning 
      and memory. Brain-derived neurotrophic factor (BDNF) is well known to be capable 
      of inducing the synthesis of activity-regulated cytoskeleton-associated protein 
      (Arc), which plays a fundamental role in modulating synaptic plasticity. Our 
      recent study has demonstrated that treatment of fibrillar Abeta at a nonlethal 
      level was sufficient to impair BDNF-induced Arc expression in cultured rat 
      cortical neurons. In this study, BDNF treatment alone induced the activation of 
      the phosphatidylinositol 3-kinase-Akt-mammlian target of rapamycin 
      (PI3K-Akt-mTOR) signaling pathway, the phosphorylation of eukaryotic initiation 
      factor 4E binding protein (4EBP1) and p70 ribosomal S6 kinase (p70S6K), the 
      dephosphorylation of eukaryotic elongation factor 2 (eEF2), and the expression of 
      Arc. Interrupting the PI3K-Akt-mTOR signaling pathway by inhibitors prevented the 
      effects of BDNF, indicating the involvement of this pathway in BDNF-induced 4EBP1 
      phosphorylation, p70S6K phosphorylation, eEF2 dephosphorylation, and Arc 
      expression. Nonlethal Abeta pretreatment partially blocked these effects of BDNF. 
      Double- immunofluorescent staining in rat cortical neurons further confirmed the 
      coexistence of eEF2 dephosphorylation and Arc expression following BDNF treatment 
      regardless of the presence of Abeta. These results reveal that, in cultured rat 
      cortical neurons, Abeta interrupts the PI3K-Akt-mTOR signaling pathway that could 
      be involved in BDNF-induced Arc expression. Moreover, this study also provides 
      the first evidence that there is a close correlation between BDNF-induced eEF2 
      dephosphorylation and BDNF-induced Arc expression. (c) 2009 Wiley-Liss, Inc.
CI  - Copyright 2009 Wiley-Liss, Inc.
FAU - Chen, Tsan-Ju
AU  - Chen TJ
AD  - Department of Physiology, Faculty of Medicine, College of Medicine, Kaohsiung 
      Medical University, Kaohsiung, Taiwan. tsanju@kmu.edu.tw
FAU - Wang, Dean-Chuan
AU  - Wang DC
FAU - Chen, Shun-Sheng
AU  - Chen SS
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Neurosci Res
JT  - Journal of neuroscience research
JID - 7600111
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Muscle Proteins)
RN  - 0 (Nol3 protein, rat)
RN  - 0 (Peptide Fragments)
RN  - 0 (amyloid beta-protein (1-42))
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (mTOR protein, rat)
RN  - EC 2.7.11.1 (Oncogene Protein v-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Amyloid beta-Peptides/pharmacology
MH  - Analysis of Variance
MH  - Animals
MH  - Animals, Newborn
MH  - Apoptosis Regulatory Proteins/*metabolism
MH  - Brain-Derived Neurotrophic Factor/pharmacology
MH  - Cells, Cultured
MH  - Cerebral Cortex/*cytology
MH  - Enzyme Inhibitors/pharmacology
MH  - Gene Expression Regulation/drug effects
MH  - Muscle Proteins/*metabolism
MH  - Neurons/*drug effects
MH  - Oncogene Protein v-akt/metabolism
MH  - Peptide Fragments/pharmacology
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Protein Kinases/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Signal Transduction/*drug effects
MH  - TOR Serine-Threonine Kinases
MH  - Time Factors
EDAT- 2009/03/21 09:00
MHDA- 2009/09/01 06:00
CRDT- 2009/03/21 09:00
PHST- 2009/03/21 09:00 [entrez]
PHST- 2009/03/21 09:00 [pubmed]
PHST- 2009/09/01 06:00 [medline]
AID - 10.1002/jnr.22057 [doi]
PST - ppublish
SO  - J Neurosci Res. 2009 Aug 1;87(10):2297-307. doi: 10.1002/jnr.22057.