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. 2010 Aug 6;26(4):338–344. doi: 10.1007/s12264-010-0131-0

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

Rui Su 1, Zhen-Yun Han 2,✉, Ji-Ping Fan 1, Yun-Ling Zhang 2
PMCID: PMC5552570  PMID: 20651816

Abstract

It is believed that amyloid-β peptide (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- and γ-secretases are all located on the lipid raft, and the meeting of them is an indispensable step for Aβ generation. Endocytosis can lead to clustering of APP, β- and γ-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 Aβ generation, by modulating free PIP2 level and actin movement, causing endocytosis.

Keywords: Alzheimer’s disease; endocytosis; myristoylated alanine-rich C kinase substrate; lipid raft; phosphatidylinositol 4, 5-bisphosphate; actin cytoskeleton

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