A possible role of myristoylated alanine-rich C kinase substrate in endocytic pathway of Alzheimer’s disease  

豆蔻酰化的富丙氨酸的蛋白激酶C的底物在阿尔茨海默病胞吞过程中的作用(英文)

作　　者：苏芮[1] 韩振蕴[2] 范吉平[1] 张允岭[2] 

机构地区：[1]中国中医科学院,北京100700 [2]北京中医药大学东方医院神经内科,北京100078

出　　处：《Neuroscience Bulletin》2010年第4期338-344,共7页神经科学通报（英文版）

基　　金：supported by the National Natural Science Foundation of China(No.30701137)

摘　　要：It is believed that amyloid-βpeptide（Aβ）plays a central role in the pathogenesis of Alzheimer’s disease（AD）.Thus,the process of amyloid precursor protein（APP）cleavage is a key event and has raised much attention in the field of AD research.It is proposed that APP,β-andγ-secretases are all located on the lipid raft,and the meeting of them is an indispensable step for Aβgeneration.Endocytosis can lead to clustering of APP,β-andγ-secretases from separate smaller lipid rafts into a larger one.On the other hand,for myristoylated alanine-rich C kinase substrate（MARCKS）,phosphorylation by protein kinase C（PKC）or interaction with Ca2＋can lead to its release from membrane into cytoplasm.This process induces the release of actins and phosphatidylinositol 4,5-bisphosphate（PIP2）,which are important factors for endocytosis.Thus,the present review proposes that MARCKS may be implicated in Aβgeneration,by modulating free PIP 2 level and actin movement,causing endocytosis.β淀粉样蛋白(amyloidβ,Aβ)在阿尔茨海默病(Alzheimer’s disease,AD)的发病过程中的重要作用已为人熟知。淀粉样前体蛋白(amyloid precursor protein,APP)的水解过程也因此成为AD研究的重点。APP、β-和γ-分泌酶都位于脂筏上,三者的相遇是产生Aβ的必要步骤,而胞吞作用则能使分布在微小脂筏上的APP、β-和γ-分泌酶集中到较大的脂筏上。另一方面,豆蔻酰化的富丙氨酸的蛋白激酶C的底物(myristoylated alanine-rich C kinase substrate,MARCKS)被蛋白激酶C磷酸化或与钙离子作用后,会离开细胞膜进入细胞质,进而引起在胞吞作用中起重要作用的肌动蛋白和4,5-二磷酸肌醇(PIP2)的释放。因此,本文提出假说,认为MARCKS通过调节自由态PIP2的水平和肌动蛋白的运动,引发胞吞作用,进而在Aβ的产生过程中起重要作用。

关 键 词：Alzheimer’s disease endocytosis myristoylated alanine-rich C kinase substrate lipid raft phosphatidylinositol 4 5-bisphosphate actin cytoskeleton 

分 类 号：R749.16[医药卫生—神经病学与精神病学]