Stabilization of intracellular trafficking and metabolism of amyloid β-protein precursor and Alcadein β by apolipoprotein E
Stabilization of intracellular trafficking and metabolism of amyloid β-protein precursor and Alcadein β by apolipoprotein E
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载脂蛋白 E 稳定淀粉样蛋白 β 蛋白前体和 Alcadein β 的细胞内运输和代谢
DOI：
10.1016/j.febslet.2015.07.017
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发表时间：
2015
期刊：
影响因子：
3.5
通讯作者：
T.
中科院分区：
文献类型：
--
作者：
Kimura;A.;Hata;S.;Suzuki;T.
淀粉样蛋白前体(Amyloidβ-Protein Producer，APP)的细胞内代谢在阿尔茨海默病(AD)的发病机制中起重要作用。Alcadeins(Alcα、Alcβ和Alcγ)是一种神经膜蛋白，其定位、代谢和细胞功能与APP相似。载脂蛋白E(ApoE)的ε4亚型是AD的主要危险因素。我们发现，载脂蛋白E的表达减弱了APP和ALCβ在细胞内的运输，导致了这两种蛋白的代谢稳定。相反，ApoE的表达促进了Alcα的胞内蛋白分解，这不是由于Alcα的初级切割增加所致。这种差异可能是由于ApoE与膜蛋白结合所致。
Intracellular metabolism of amyloid β-protein precursor (APP) is important for the pathogenesis of Alzheimer’s disease (AD). Alcadeins (Alcα, Alcβ, and Alcγ) are neural membrane proteins similar to APP in their localization, metabolism, and cellular function. Isoform ε4 of apolipoprotein E (ApoE) is a major risk factor for AD. We found that ApoE expression attenuated intracellular trafficking of APP and Alcβ, resulting in metabolic stabilization of both proteins. By contrast, Alcα intracellular proteolysis was facilitated by ApoE expression, which was not due to an increase in the primary cleavage of Alcα. This difference may result from binding of ApoE to membrane proteins.