beta-Arrestin1 regulates gamma-secretase complex assembly and modulates amyloid-beta pathology

	beta-Arrestin1 regulates gamma-secretase complex assembly and modulates amyloid-beta pathology
	Liu, XS; Zhao, XH; Zeng, XL; Bossers, K; Swaab, DF; Zhao, J; Pei, G
刊名	CELL RESEARCH
	2013
卷号	23 期号:3 页码:351-365
关键词	Alzheimer's disease beta-arrestin1 APH-1 gamma-secretase
通讯作者	Pei, G (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, State Key Lab Cell Biol, Shanghai 200031, Peoples R China.,jzhao@sibs.ac.cn ; gpei@sibs.ac.cn
英文摘要	Alzheimer's disease (AD) is a progressive and complex neurodegenerative disease in which the gamma-secretase-mediated amyloid-beta (A beta) pathology plays an important role. We found that a multifunctional protein, beta-arrestin1, facilitated the formation of NCT/APH-1 (anterior pharynx-defective phenotype 1) precomplex and mature gamma-secretase complex through its functional interaction with APH-1. Deficiency of beta-arrestin1 or inhibition of binding of beta-arrestin1 with APH-1 by small peptides reduced A beta production without affecting Notch processing. Genetic ablation of beta-arrestin1 diminished A beta pathology and behavioral deficits in transgenic AD mice. Moreover, in brains of sporadic AD patients and transgenic AD mice, the expression of beta-arrestin1 was upregulated and correlated well with neuropathological severity and senile A beta plaques. Thus, our study identifies a regulatory mechanism underlying both gamma-secretase assembly and AD pathogenesis, and indicates that specific reduction of A beta pathology can be achieved by regulation of the gamma-secretase assembly.
学科主题	Cell Biology
类目[WOS]	Cell Biology
关键词[WOS]	ALZHEIMERS-DISEASE ; PRECURSOR PROTEIN ; INTRACELLULAR DOMAIN ; CELL-SURFACE ; PRESENILIN ; MICE ; NICASTRIN ; CLEAVAGE ; NOTCH ; SUBCOMPLEX
收录类别	SCI
语种	英语
WOS记录号	WOS:000316375000009
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/361]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Liu, XS,Zhao, XH,Zeng, XL,et al. beta-Arrestin1 regulates gamma-secretase complex assembly and modulates amyloid-beta pathology[J]. CELL RESEARCH,2013,23(3):351-365.
APA	Liu, XS.,Zhao, XH.,Zeng, XL.,Bossers, K.,Swaab, DF.,...&Pei, G.(2013).beta-Arrestin1 regulates gamma-secretase complex assembly and modulates amyloid-beta pathology.CELL RESEARCH,23(3),351-365.
MLA	Liu, XS,et al."beta-Arrestin1 regulates gamma-secretase complex assembly and modulates amyloid-beta pathology".CELL RESEARCH 23.3(2013):351-365.