TrkA pathway activation induced by amyloid-beta (Abeta)

被引：32

作者：

Bulbarelli, Alessandra ^{[1
]}

Lonati, Elena ^{[1
]}

Cazzaniga, Emanuela ^{[1
]}

Re, Francesca ^{[1
]}

Sesana, Silvia ^{[1
]}

Barisani, Donatella ^{[1
]}

Sancini, Giulio ^{[1
]}

Mutoh, Tatsuro ^{[2
]}

Masserini, Massimo ^{[1
]}

机构：

[1] Univ Milano Bicocca, Dept Expt Med, I-20052 Monza, MI, Italy

[2] Fujita Hlth Univ, Sch Med, Dept Neurol, Toyoake, Aichi 47011, Japan

来源：

MOLECULAR AND CELLULAR NEUROSCIENCE | 2009年 / 40卷 / 03期

关键词：

Alzheimer; Amyloid beta peptide; NGF; TrkA; AKT; GSK-3; beta; NERVE GROWTH-FACTOR; CULTURED HIPPOCAMPAL-NEURONS; LONG-TERM POTENTIATION; APOPTOTIC CELL-DEATH; ALZHEIMERS-DISEASE; NEUROTROPHIC FACTOR; PC12; CELLS; IN-VITRO; CEREBRAL-ISCHEMIA; SIGNALING PATHWAY;

D O I：

10.1016/j.mcn.2008.12.006

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Amyloid-beta (A beta), a cytotoxic fragment of Amyloid precursor Protein (APP), has been implicated in the etiopathogenesis of Alzheimer's disease (AD). Since several neurotrophins signalling pathways may be activated in response to toxic insults, we investigated whether a similar response is triggered also by A beta. After A beta (25-35) peptide administration to Cultured rat hippocampal neurons, the nerve growth factor (NGF) and its receptor (TrkA) rnRNA expression is Up-regulated. Moreover, we observe an increased cellular TrkA expression (4.5 fold) and NGF release in the culture medium (5-fold). Concomitantly,TrkA, Akt and glycogen synthase kinase 3 beta (Gsk3 beta) phosphorylation significantly increase. Interestingly, when cells were treated with A beta (25-35) in the presence of blocking antibody against NGF, only a partial TrkA activation (2-fold) was observed. These results have been confirmed by using pathophysiological A beta (1-42) oligomers. Our data provide the evidence that A beta induces the TrkA pathway activation directly by itself and indirectly promoting NGF secretion. (C) 2008 Elsevier Inc. All rights reserved.

引用

页码：365 / 373

页数：9

共 59 条

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