Formononetin attenuates Aβ25-35-induced cytotoxicity in HT22 cells via PI3K/Akt signaling and non-amyloidogenic cleavage of APP

被引:29
作者
Chen, Lizhi [1 ]
Ou, Shanshan [1 ]
Zhou, Lingqi [1 ]
Tang, Hai [1 ]
Xu, Jie [1 ]
Guo, Kaihua [1 ]
机构
[1] Sun Yat Sen Univ, Zhongshan Med Coll, Dept Anat, Guangzhou 510080, Guangdong, Peoples R China
基金
中国国家自然科学基金;
关键词
Alzheimer's disease; beta-amyloid; Formononetin; APP; ER alpha; PI3K/Akt; BREAST-CANCER CELLS; ALZHEIMERS-DISEASE; UP-REGULATION; PATHWAY; PROTEIN; ACTIVATION; ALPHA; MECHANISMS; APOPTOSIS; SECRETASE;
D O I
10.1016/j.neulet.2016.12.064
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Amyloid beta (A beta) is the main component of the amyloid plaques that accumulate in the brains of Alzheimer patients. Here, we reported the protective role of Formononetin (Form) against A beta(25-35)-induced neurotoxicity in HT22 cells. We found that Form significantly increased the viability of HT22 cells but decreased the cell apoptosis when challenging with A beta(25-35). The inhibitory effects of Form were associated with PI3K/Akt signaling pathway as PI3K inhibitor (LY294002) or ER alpha specific inhibitor (MPP) blocked the effects. Form also accelerated the non-amyloidogenic process of amyloid precursor protein (APP) by enhancing alpha-secretase activity and sAPP alpha release. Altogether, our findings may provide a novel therapeutic target to treat AD sufferers. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:36 / 42
页数:7
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