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芒柄花黄素通过PI3K/Akt信号通路和APP的非淀粉样生成性切割减轻Aβ诱导的HT22细胞毒性。

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

作者信息

Chen Lizhi, Ou Shanshan, Zhou Lingqi, Tang Hai, Xu Jie, Guo Kaihua

机构信息

Department of Anatomy, Zhongshan Medical College, Sun Yat-Sen University, Guangzhou, China.

Department of Anatomy, Zhongshan Medical College, Sun Yat-Sen University, Guangzhou, China.

出版信息

Neurosci Lett. 2017 Feb 3;639:36-42. doi: 10.1016/j.neulet.2016.12.064. Epub 2016 Dec 26.

DOI:10.1016/j.neulet.2016.12.064
PMID:28034780
Abstract

Amyloid beta (Aβ) 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 Aβ-induced neurotoxicity in HT22 cells. We found that Form significantly increased the viability of HT22 cells but decreased the cell apoptosis when challenging with Aβ The inhibitory effects of Form were associated with PI3K/Akt signaling pathway as PI3K inhibitor (LY294002) or ERα specific inhibitor (MPP) blocked the effects. Form also accelerated the non-amyloidogenic process of amyloid precursor protein (APP) by enhancing α-secretase activity and sAPPα release. Altogether, our findings may provide a novel therapeutic target to treat AD sufferers.

摘要

β-淀粉样蛋白(Aβ)是在阿尔茨海默病患者大脑中积累的淀粉样斑块的主要成分。在此,我们报道了刺芒柄花素(Form)对Aβ诱导的HT22细胞神经毒性的保护作用。我们发现,当用Aβ刺激时,刺芒柄花素显著提高了HT22细胞的活力,但减少了细胞凋亡。刺芒柄花素的抑制作用与PI3K/Akt信号通路有关,因为PI3K抑制剂(LY294002)或雌激素受体α特异性抑制剂(MPP)阻断了这些作用。刺芒柄花素还通过增强α-分泌酶活性和sAPPα释放来加速淀粉样前体蛋白(APP)的非淀粉样生成过程。总之,我们的研究结果可能为治疗阿尔茨海默病患者提供一个新的治疗靶点。

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