Amyloid-B peptides stimulate the expression of the p75NTR neurotrophin receptor in SH-SY5Y human neuroblastoma cells and AD-transgenic mice

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DOIResolve DOI: http://doi.org/10.3233/JAD-2010-1288
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TypeArticle
Journal titleJournal of Alzheimer’s Disease
Volume19
Issue3
Pages915925; # of pages: 11
SubjectAlzheimer’s disease; amyloid-β peptides; p75NTR (neurotrophin receptor); SH-SY5Y human neuroblastomas; transgenic mice
AbstractThe progression toward end-stage Alzheimer’s disease (AD) in the aging brain is driven by accumulating amyloid-β (Aβ) 1−42 oligomers that is accompanied by the downregulation of the Trk Aneurotrophin receptor and by either upregulation or at least maintenance of the p75 neurotrophin receptor (p75NTR), which can be stimulated by the accumulating Aβ1−42 peptides. Here we show that Aβ1−42 and its active fragment Aβ25−35, but not Aβ42−1, can at least double the level of p75NTR receptors in the membranes of model SH-SY5Y human neuroblastoma cells. We also show that p75NTR is upregulated in the hippocampi of two strains of AD transgenic mice. Specifically, the level of the p75NTR receptor in the hippocampal membranes from 12–15 month-old AD-triple transgenic mice (3xTg-AD) harboring PS1M146V , AβPPSwe, and tau P301L was nearly twice that in hippocampal membranes from age-matched wild-type mice. Similarly, the level of p75NTR receptor in 7 month-old B6.Cg-Tg AD mice harboring PSEN1dE9 and AβPPSwe was also increased above the level in the corresponding wild-type mice. This increase correlated with the age-dependent rise in Aβ1−42 levels in the AD mice. Thus, it appears that it could be the accumulating Aβ1−42 that increases or at least prevents the downregulation of p75NTR receptors in key parts of AD brains. It is possible that when the Aβ1−42 accumulation reaches a critical level in the brain on the way to late-onset AD, the Aβ1−42-induced p75NTR receptor signaling starts a vicious cycle that accelerates AD development because of the activated receptors’ recently shown ability to stimulate Aβ1−42 production.
Publication date
LanguageEnglish
AffiliationNRC Institute for Biological Sciences; National Research Council Canada
Peer reviewedYes
NPARC number17479679
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Record identifier481fa4fc-40bc-429c-a41b-caf5d98d8a08
Record created2011-03-30
Record modified2016-05-09
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