Arctigenin Effectively Ameliorates Memory Impairment in Alzheimer's Disease Model Mice Targeting Both β-Amyloid Production and Clearance

被引：208

作者：

Zhu, Zhiyuan ^{[1
]}

Yan, Jianming ^{[1
]}

Jiang, Wei ^{[1
]}

Yao, Xin-gang ^{[1
]}

Chen, Jing ^{[1
]}

Chen, Lili ^{[1
]}

Li, Chenjing ^{[1
]}

Hu, Lihong ^{[1
]}

Jiang, Hualiang ^{[1
]}

Shen, Xu ^{[1
]}

机构：

[1] Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China

来源：

JOURNAL OF NEUROSCIENCE | 2013年 / 33卷 / 32期

基金：

中国博士后科学基金; 中国国家自然科学基金;

关键词：

ACTIVATED PROTEIN-KINASE; MOUSE MODEL; THERAPEUTIC TARGET; BACE1; EXPRESSION; MAMMALIAN TARGET; LIFE-SPAN; IN-VITRO; AUTOPHAGY; AMPK; PHOSPHORYLATION;

D O I：

10.1523/JNEUROSCI.4790-12.2013

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Alzheimer's disease (AD) chiefly characterizes a progressively neurodegenerative disorder of the brain, and eventually leads to irreversible loss of intellectual abilities. The beta-amyloid (A beta)-induced neurodegeneration is believed to be the main pathological mechanism of AD, and A beta production inhibition or its clearance promotion is one of the promising therapeutic strategies for anti-AD research. Here, we report that the natural product arctigenin from Arctium lappa (L.) can both inhibit A beta production by suppressing beta-site amyloid precursor protein cleavage enzyme 1 expression and promote A beta clearance by enhancing autophagy through AKT/mTOR signaling inhibition and AMPK/Raptor pathway activation as investigated in cells and APP/PS1 transgenic AD model mice. Moreover, the results showing that treatment of arctigenin in mice highly decreased A beta formation and senile plaques and efficiently ameliorated AD mouse memory impairment strongly highlight the potential of arctigenin in anti-AD drug discovery.

引用

页码：13138 / 13149

页数：12

共 67 条

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