Altered localization of amyloid precursor protein under endoplasmic reticulum stress
Altered localization of amyloid precursor protein under endoplasmic reticulum stress
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DOI：
10.1016/j.bbrc.2006.03.173
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发表时间：
2006-06-02
影响因子：
3.1
通讯作者：
Takeda, M
中科院分区：
文献类型：
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作者：
Kudo, T;Okumura, M;Takeda, M
最近的研究表明，内质网应激与阿尔茨海默病的发病机制有关。因此，根据淀粉样蛋白级联假说，我们试图研究内质网应激油淀粉样β蛋白(Aβ)生成的影响。在本研究中，我们发现内质网应激改变了淀粉样前体蛋白(APP)从分泌途径的晚期到早期的定位，并通过削减β和伽马来降低Aβ40和Aβ42的释放水平。瞬时转染Bip/GRP78还可引起APP的移位和Aβ分泌的减少。结果表明，内质网应激反应促进了Bip/GRP78与APP的结合，从而使其保留在早期的隔室中，而不是Aβ的适宜切割位置。这些发现提示，内质网应激过程中Bip/GRP78的诱导可能是Aβ生成的调节机制之一。(C)2006 Elsevier Inc.保留所有权利。
Recent reports have shown that the endoplasmic reticulum (ER) stress is relevant to the pathogenesis of Alzheimer disease. Following the amyloid cascade hypothesis, we therefore attempted to investigate the effects of ER stress oil amyloid-beta peptide (A beta) generation. In this study, we found that ER stress altered the localization of amyloid precursor protein (APP) from late compartments to early compartments of the secretory pathway, and decreased the level of A beta 40 and A beta 42 release by beta- and gamma-cutting. Transient transfection with BiP/GRP78 also caused a shift of APP and a reduction in A beta secretion. It was revealed that the ER stress response facilitated binding of BiP/GRP78 to APP, thereby causing it to be retained in the early compartments apart from a location suitable for the cleavages of A beta. These findings suggest that induction of BiP/GRP78 during ER stress may be one of the regulatory mechanisms of A beta generation. (c) 2006 Elsevier Inc. All rights reserved.