It is believed that amyloid-beta peptide (Abeta) 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, beta- and gamma-secretases are all located on the lipid raft, and the meeting of them is an indispensable step for Abeta generation. Endocytosis can lead to clustering of APP, beta- and gamma-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 Ca(2+) 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 Abeta generation, by modulating free PIP2 level and actin movement, causing endocytosis.
β淀粉样蛋白(amyloid β, 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。