SCG10通过促进淀粉样前体蛋白APP转运到细胞表面增加其α型加工

滕俊琳 王晶晶

摘 要：淀粉样前体蛋白（APP）的β切割所产生的Aβ阿尔茨海默病（Alzheimer's disease，AD）致病因子。APP的加工方式与特定的亚细胞区域相关，并受到多个与转运相关的因子的影响。我们实验结果显示SCG10直接与APP的胞内结构域KFFEQ基序相结合促进APP的α型加工过程。敲低SCG10导致α型加工产物sAPPα和CTFα的减少，从而增加了Aβ1-40和Aβ1-42的量。增加SCG10的表达量，可以促进APP从高尔基体运往细胞表面，减少β切割，降低Aβ的量。在APPswe/PS1dE9转基因小鼠海马中增加SCG10的表达量能够减少该部位Aβ积累和淀粉样斑块形成。综上所述，这些结果表明SCG10在预防和治疗AD中有潜在的作用。

关键词：淀粉样前体蛋白 Aβ阿尔茨海默病 sAPPα SCG10

SCG10 Promotes Non-amyloidogenic Processing of Amyloid Precursor Protein by Facilitating Its Trafficking to the Cell Surface

Teng Junlin Wang Jingjing

（Peking University）

Abstract：The processing of amyloid precursor protein （APP） is a key event in the pathogenesis of Alzheimersdisease. Since certain cleavage pathways tend to occur in particular subcellular compartments， the processing of APP is greatly influenced by factors which regulate its trafficking. Here we report that SCG10 directly interacts with the KFFEQ motif of the APP intracellular domain and promotes the non-amyloidogenic processing of APP. Knockdown of SCG10 led to decreases in α cleavage products， sAPPα and CTFα， while increases of both Aβ1-40 and Aβ1-42. Elevation of SCG10 induced APP accumulation in post-Golgi vesicles and on the cell surface by facilitating its secretory pathway. In addition， the APP processing was dependent on the palmitoylation-mediated membrane-anchoring of SCG10. Furthermore， elevation of SCG10 reduced Aβ accumulation and amyloid plaque formation in the hippocampus of APPswe/PS1dE9 mice. Taken together， theseresults show that SCG10 has a potential role in preventing and treating Alzheimers disease.

Key Words：APP； AD； sAPPα； SCG10； Anterograde transport

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