Activation of beta(2)-adrenergic receptor stimulates gamma-secretase activity and accelerates amyloid plaque formation

	Activation of beta(2)-adrenergic receptor stimulates gamma-secretase activity and accelerates amyloid plaque formation
	Ni, YX; Zhao, XH; Bao, GB; Zou, L; Teng, L; Wang, Z; Song, M; Xiong, JX; Bai, Y; Pei, G
刊名	NATURE MEDICINE
	2006
卷号	12 期号:12 页码:1390-1396
通讯作者	Pei, G (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Mol Cell Biol Lab, Inst Biochem & Cell Biol, 320 Yue Yang Rd, Shanghai 200031, Peoples R China.,gpei@sibs.ac.cn
英文摘要	Amyloid plaque is the hallmark and primary cause of Alzheimer disease. Mutations of presenilin-1, the gamma-secretase catalytic subunit, can affect amyloid-beta (A beta) production and Alzheimer disease pathogenesis. However, it is largely unknown whether and how c-secretase activity and amyloid plaque formation are regulated by environmental factors such as stress, which is mediated by receptors including beta(2)-adrenergic receptor (beta(2)-AR). Here we report that activation of beta(2)-AR enhanced gamma-secretase activity and thus A beta production. This enhancement involved the association of beta(2)-AR with presenilin-1 and required agonist-induced endocytosis of beta(2)-AR and subsequent trafficking of gamma-secretase to late endosomes and lysosomes, where A beta production was elevated. Similar effects were observed after activation of delta-opioid receptor. Furthermore, chronic treatment with beta(2)-AR agonists increased cerebral amyloid plaques in an Alzheimer disease mouse model. Thus, beta(2)-AR activation can stimulate c-secretase activity and amyloid plaque formation, which suggests that abnormal activation of beta(2)-AR might contribute to A beta accumulation in Alzheimer disease pathogenesis.
学科主题	Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine
类目[WOS]	Biochemistry & Molecular Biology ; Cell Biology ; Medicine, Research & Experimental
关键词[WOS]	ALZHEIMERS-DISEASE ; PRECURSOR PROTEIN ; A-BETA ; TRANSGENIC MICE ; ENDOCYTIC PATHWAY ; PRESENILIN ; BRAIN ; STRESS ; OLIGOMERIZATION ; TRAFFICKING
收录类别	SCI
语种	英语
WOS记录号	WOS:000242618200019
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/1782]
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	Ni, YX,Zhao, XH,Bao, GB,et al. Activation of beta(2)-adrenergic receptor stimulates gamma-secretase activity and accelerates amyloid plaque formation[J]. NATURE MEDICINE,2006,12(12):1390-1396.
APA	Ni, YX.,Zhao, XH.,Bao, GB.,Zou, L.,Teng, L.,...&Pei, G.(2006).Activation of beta(2)-adrenergic receptor stimulates gamma-secretase activity and accelerates amyloid plaque formation.NATURE MEDICINE,12(12),1390-1396.
MLA	Ni, YX,et al."Activation of beta(2)-adrenergic receptor stimulates gamma-secretase activity and accelerates amyloid plaque formation".NATURE MEDICINE 12.12(2006):1390-1396.