Dissociation of Akt/PKB and ribosomal S6 kinase signaling markers in a transgenic mouse model of Alzheimer's disease.
Previous studies demonstrated that the PKR (double-stranded RNA-activated protein kinase) pathway was activated while the mTOR (mammalian target of rapamycin) pathway was inhibited in Alzheimer's disease (AD). Here, we analysed upstream and downstream factors of mTOR in brain of APP(SL)/PS1 KI mice displaying a massive neuronal loss in hippocampus. While mTOR levels were not modified, we found a great activation of Akt with a robust accumulation of P-Akt((T308)) in non-apoptotic neurons at 6 months of age. At the opposite, a significant decrease of the p70/85S6K activation was observed in brain of PS1 KI and APP(SL)/PS1 KI mice with a very weak or no nucleocytoplasmic P-p70/85S6K((T389)) staining in apoptotic neurons of APP(SL)/PS1 KI mice. Furthermore, the activation of Erk1/2, 4E-BP1 and p70S6K((T421/S424)) (substrate of Erk1/2), except eIF4E, was not modified. These findings demonstrate a clear dissociation between Akt and ribosomal S6K signaling markers in these mice which could be involved in the AD pathological process.
Damjanac
Milena
M
Research Group on Brain Aging (EA 3808) University of Poitiers, 6 rue de la Milétrie BP 199, 86034 Poitiers, Cedex, France.
Rioux Bilan
Agnès
A
Paccalin
Marc
M
Pontcharraud
Raymond
R
Fauconneau
Bernard
B
Hugon
Jacques
J
Page
Guylène
G
D000367:Age Factors; D000544:Alzheimer Disease / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D001921:Brain / Q000378:metabolism*; D004195:Disease Models, Animal; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D020287:In Situ Nick-End Labeling; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000378:metabolism; D051058:Oncogene Protein v-akt / Q000378:metabolism*; D053764:Presenilin-1 / Q000235:genetics; D019893:Ribosomal Protein S6 Kinases / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*
D016564:Amyloid beta-Protein Precursor; D009419:Nerve Tissue Proteins; D053764:Presenilin-1; D051058:Oncogene Protein v-akt; D019893:Ribosomal Protein S6 Kinases