The progression toward end-stage Alzheimer's disease (AD) in the aging brain is driven by accumulating amyloid-beta (Abeta)1-42 oligomers that is accompanied by the downregulation of the Trk A neurotrophin receptor and by either upregulation or at least maintenance of the p75 neurotrophin receptor (p75NTR), which can be stimulated by the accumulating Abeta1-42 peptides. Here we show that Abetae fragment Abeta25-35, but not Abeta42-1, 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 monthold AD-triple transgenic mice (3xTg-AD) harboring PS1_M146V, AbetaPP_Swe, 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 AbetaPP_Swe was also increased above the level in the corresponding wild-type mice. This increase correlated with the age-dependent rise in Abeta1-42 levels in the AD mice. Thus, it appears that it could be the accumulating Abeta1-42 that increases or at least prevents the downregulation of p75NTR receptors in key parts of AD brains. It is possible that when the Abeta1-42 accumulation reaches a critical level in the brain on the way to late-onset AD, the Abeta1-42-induced p75NTR receptor signaling starts a vicious cycle that accelerates AD development because of the activated receptors' recently shown ability to stimulate Abeta1-42 production. PMID: 19920315 [Pu

Amyloid-beta Peptides Stimulate the Expression of the p75NTR / Neurotrophin Receptor in SHSY5Y Human Neuroblastoma Cells and AD Transgenic Mice.

ARMATO, Ubaldo;
2010

Abstract

The progression toward end-stage Alzheimer's disease (AD) in the aging brain is driven by accumulating amyloid-beta (Abeta)1-42 oligomers that is accompanied by the downregulation of the Trk A neurotrophin receptor and by either upregulation or at least maintenance of the p75 neurotrophin receptor (p75NTR), which can be stimulated by the accumulating Abeta1-42 peptides. Here we show that Abetae fragment Abeta25-35, but not Abeta42-1, 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 monthold AD-triple transgenic mice (3xTg-AD) harboring PS1_M146V, AbetaPP_Swe, 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 AbetaPP_Swe was also increased above the level in the corresponding wild-type mice. This increase correlated with the age-dependent rise in Abeta1-42 levels in the AD mice. Thus, it appears that it could be the accumulating Abeta1-42 that increases or at least prevents the downregulation of p75NTR receptors in key parts of AD brains. It is possible that when the Abeta1-42 accumulation reaches a critical level in the brain on the way to late-onset AD, the Abeta1-42-induced p75NTR receptor signaling starts a vicious cycle that accelerates AD development because of the activated receptors' recently shown ability to stimulate Abeta1-42 production. PMID: 19920315 [Pu
Alzheimer disease; p75 neurotrophin receptor; transgenic mouse; amyloid-beta peptides
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11562/339973
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