| DOI | Trouver le DOI : https://doi.org/10.3233/JAD-2012-120046 |
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| Auteur | Rechercher : Ito, S.1; Rechercher : Ménard, M.1; Rechercher : Atkinson, T.1; Rechercher : Gaudet, C.1; Rechercher : Brown, L.1; Rechercher : Whitfield, J.1; Rechercher : Chakravarthy, B.1 |
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| Affiliation | - Conseil national de recherches du Canada. Institut des sciences biologiques du CNRC
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| Format | Texte, Article |
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| Sujet | amyloid beta protein[1-42]; neurotrophin receptor p75; oligomer; somatomedin C receptor; Alzheimer disease; animal experiment; animal model; animal tissue; disease model; female; hippocampus; human cell; in vivo study; male; microinjection; mouse; neuroblastoma cell; protein expression; protein phosphorylation; transgenic mouse; wild type; Amyloid beta-Peptides; Cell Line, Tumor; Female; Gene Expression Regulation; Hippocampus; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Peptide Fragments; Receptor, IGF Type 1; Receptors, Nerve Growth Factor; Signal Transduction |
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| Résumé | The p75 neurotrophin receptor (p75NTR) has been thought to play a critical role in amyloid-β peptide (Aβ)-mediated neurodegeneration and Aβ metabolism in Alzheimer's disease (AD) brains. Our previous report showed that membrane-associated p75NTR protein expression was significantly increased in the hippocampi of two different strains of transgenic AD mice and was associated with the age-dependent elevation of Aβ1-42 levels. Here, we provide evidence that the Aβ1-42 oligomers known as ADDLs (Aβ-derived diffusible ligands) induce p75NTR protein expression through insulin-like growth factor 1 receptor (IGF-1R) phosphorylation in SH-SY5Y human neuroblastoma cells. An in vivo microinjection study demonstrated that microinjected ADDLs increased the p75NTR protein expression by 1.4-fold in the ipsilateral hippocampus compared to the contralateral hippocampus. In addition, ADDLs microinjected into mouse hippocampi facilitated IGF-1R phosphorylation within 30 min and the co-administration of picropodophyllin, an IGF-1R kinase inhibitor, blocked ADDLs-induced p75NTR expression. We examined the possible involvement of IGF-1R in the increased p75NTR protein expression in the hippocampi of 6-month-old AβPPswe/PS1dE9 AD model mice that had accumulated significant amounts of Aβ1-42 and showed significantly higher p75NTR expression than age-matched wild-type mice. We found that IGF-1R phosphorylation in these transgenic mice was higher than that in the wild-type mice. These findings indicate that Aβ1-42 oligomers stimulate the p75NTR protein expression in the hippocampus through IGF-1R signaling. Thus, Aβ1-42 oligomers-mediated IGF-1R activation may trigger an increase in p75NTR protein expression in the hippocampus of AD brain during the early stages of disease development. © 2012-IOS Press and the authors. All rights reserved. |
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| Date de publication | 2012 |
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| Dans | |
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| Langue | anglais |
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| Publications évaluées par des pairs | Oui |
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| Numéro NPARC | 21269274 |
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| Exporter la notice | Exporter en format RIS |
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| Signaler une correction | Signaler une correction (s'ouvre dans un nouvel onglet) |
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| Identificateur de l’enregistrement | b39b0d6c-9fc8-4279-ae5d-e20c207c68c4 |
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| Enregistrement créé | 2013-12-12 |
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| Enregistrement modifié | 2020-04-21 |
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