β-Arrestinl regulates γ-secretase complex assembly and modulates amyloid-β pathology  

作　　者：Xiaosong Liu Xiaohui Zhao Xianglu Zeng Koen Bossers Dick F Swaab Jian Zhao Gang Pei 

机构地区：[1]State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences [2]Graduate School of the Chinese Academy of Sciences, Shanghai 200031, China [3]Netherlands Institute for Neuroscience, Meibergdreef 47, 1105 BA Amsterdam, The Netherlands [4]School of Life Science and Technology, Tongji University, Shanghai 200092, China

出　　处：《Cell Research》2013年第3期351-365,共15页细胞研究（英文版）

摘　　要：Alzheimer＇s disease （AD） is a progressive and complex neurodegenerative disease in which the γ-secretase- mediated amyloid-β （Aβ） pathology plays an important role. We found that a multifunctional protein, β-arrestinl, facilitated the formation of NCT/APH-1 （anterior pharynx-defective phenotype 1） precomplex and mature T-secretase complex through its functional interaction with APH-1. Deficiency of β-arrestinl or inhibition of binding of β-arrestinl with APH-1 by small peptides reduced Aβ production without affecting Notch processing. Genetic ablation of β-arrestinl diminished Aβ pathology and behavioral deficits in transgenic AD mice. Moreover, in brains of sporadic AD patients and transgenic AD mice, the expression of β-arrestinl was upregulated and correlated well with neuropathological severity and senile Aβ plaques. Thus, our study identifies a regulatory mechanism underlying both y-secretase assembly and AD pathogenesis, and indicates that specific reduction of Aβ pathology can be achieved by regulation of the γ-secretase assembly.

关 键 词：Alzheimer＇s disease β-arrestinl APH- 1 Γ-SECRETASE 

分 类 号：Q517[生物学—生物化学] S763.712.4[农业科学—森林保护学]