Possible roles of amyloid intracellular domain of amyloid precursor protein.
Possible roles of amyloid intracellular domain of amyloid precursor protein.
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DOI：
10.5483/bmbrep.2010.43.10.656
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发表时间：
2010-10
期刊：
影响因子：
3.8
通讯作者：
Keun-A Chang;Y. Suh
中科院分区：
文献类型：
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作者：
Keun-A Chang;Y. Suh
淀粉样蛋白前体蛋白（APP）在阿尔茨海默病（AD）的发病过程中起着至关重要的作用，它被γ /epsilon分泌酶活性切割，并导致不同长度的APP胞内c端结构域（AICD）的产生。尽管AICD体积小，半衰期短，但它已成为AD发病机制研究的焦点。最近，研究表明，AICD与不同的细胞内结合伙伴（“适配器蛋白”）结合，从而调节其稳定性和细胞定位。在接头蛋白的选择方面，磷酸化似乎起着重要的作用。AICD及其各种接头蛋白被认为参与多种细胞事件，包括调控基因转录、凋亡、钙信号、生长因子和NF-κB通路的激活，以及APP的产生、运输和加工，以及细胞骨架动力学的调节。本文就AICD在包括AD在内的神经退行性疾病发病机制中的可能作用进行综述。
Amyloid precursor protein (APP), which is critically involved in the pathogenesis of Alzheimer's disease (AD), is cleaved by gamma/epsilon-secretase activity and results in the generation of different lengths of the APP Intracellular C-terminal Domain (AICD). In spite of its small size and short half-life, AICD has become the focus of studies on AD pathogenesis. Recently, it was demonstrated that AICD binds to different intracellular binding partners ('adaptor protein'), which regulate its stability and cellular localization. In terms of choice of adaptor protein, phosphorylation seems to play an important role. AICD and its various adaptor proteins are thought to take part in various cellular events, including regulation of gene transcription, apoptosis, calcium signaling, growth factor, and NF-κB pathway activation, as well as the production, trafficking, and processing of APP, and the modulation of cytoskeletal dynamics. This review discusses the possible roles of AICD in the pathogenesis of neurodegenerative diseases including AD.