1 China Academy of Chinese Medical Sciences, Beijing 100700, China 
2 Beijing University of Traditional Chinese Medicine subsidiary Dongfang Hospital, Beijing 100078, China

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

[SpringerLink]