Inhibition of Aβ production by NF-κB inhibitors
Inhibition of Aβ production by NF-κB inhibitors
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DOI：
10.1016/j.neulet.2006.12.029
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发表时间：
2007-03-19
影响因子：
2.5
通讯作者：
Mullan, Michael
中科院分区：
文献类型：
--
作者：
Paris, Daniel;Patel, Nikunj;Mullan, Michael
转录因子核因子KB（NF-κ B B）在神经系统中广泛表达，并且在阿尔茨海默病（AD）脑中在弥漫性β-淀粉样斑块附近的神经元核中观察到增加的NF-κ B免疫反应性。β-淀粉样蛋白（A β）肽是老年斑的主要成分，并且已知刺激NF-κ B活性。在本研究中，我们使用过表达β-淀粉样前体蛋白（APP）的CHO细胞研究了各种NF-κ B抑制剂对A β（1 - 40）、A β（1 - 42）、分泌型APP（sAPP β和sAPP α）和APP C-末端片段（APP-CTF）产生的影响。我们的数据显示NF-κ B抑制剂降低A β（1 - 40）和A β（1 - 42）的产生。此外，我们发现一些NF-κ B抑制剂降低sAPP β和APP-CTF β，表明它们降低APP的β-分泌酶裂解。总之，我们的数据表明，NF-κ B抑制剂可能对AD病理学治疗具有重要的治疗意义，不仅通过阻断炎症过程，而且通过直接抑制A β肽的产生。(c)2006爱思唯尔爱尔兰有限公司保留所有权利。
The transcription factor nuclear factor KB (NF-kappa B) is widely expressed in the nervous system and increased NF-kappa B immunoreactivity has been observed in Alzheimer's disease (AD) brains in the nuclei of neuron within the vicinity of diffuse beta-amyloid plaques. beta-Amyloid (A beta) peptides are the main constituent of senile plaques and are known to stimulate NF-kappa B activity. In the present study, we investigated the effect of various NF-kappa B inhibitors on the production of A beta(1-40), A beta(1-42), secreted APP (sAPP beta and sAPP alpha) and APP C-terminal fragments (APP-CTF) using CHO cells overexpressing the beta-amyloid precursor protein (APP). Our data show that NF-kappa B inhibitors decrease both A beta(1-40) and A beta(1-42) production. In addition, we show that some NF-kappa B inhibitors decrease sAPP beta and APP-CTF beta suggesting that they reduce the beta-secretase cleavage of APP. Altogether our data suggest that NF-kappa B inhibitors may be of therapeutic importance for the treatment of AD pathology not only by blocking inflammatory processes but also by directly inhibiting the production of A beta peptides. (c) 2006 Elsevier Ireland Ltd. All rights reserved.