Disease Models & Mechanisms 2014-12-01

Triptolide treatment reduces Alzheimer's disease (AD)-like pathology through inhibition of BACE1 in a transgenic mouse model of AD.

Qi Wang, Bing Xiao, Shuqin Cui, Hailong Song, Yanjing Qian, Lin Dong, Haiting An, Yanqiu Cui, Wenjing Zhang, Yi He, Jianliang Zhang, Jian Yang, Feilong Zhang, Guanzheng Hu, Xiaoli Gong, Zhen Yan, Yan Zheng, Xiaomin Wang

Index: Dis. Model Mech. 7(12) , 1385-95, (2014)

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Abstract

The complex pathogenesis of Alzheimer's disease (AD) involves multiple contributing factors, including amyloid β (Aβ) peptide accumulation, inflammation and oxidative stress. Effective therapeutic strategies for AD are still urgently needed. Triptolide is the major active compound extracted from Tripterygium wilfordii Hook.f., a traditional Chinese medicinal herb that is commonly used to treat inflammatory diseases. The 5-month-old 5XFAD mice, which carry five familial AD mutations in the β-amyloid precursor protein (APP) and presenilin-1 (PS1) genes, were treated with triptolide for 8 weeks. We observed enhanced spatial learning performances, and attenuated Aβ production and deposition in the brain. Triptolide also inhibited the processing of amyloidogenic APP, as well as the expression of βAPP-cleaving enzyme-1 (BACE1) both in vivo and in vitro. In addition, triptolide exerted anti-inflammatory and anti-oxidative effects on the transgenic mouse brain. Triptolide therefore confers protection against the effects of AD in our mouse model and is emerging as a promising therapeutic candidate drug for AD. © 2014. Published by The Company of Biologists Ltd.