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Glaucocalyxin A as a natural product increases amyloid β clearance and decreases tau phosphorylation involving the mammalian target of rapamycin signaling pathway

Zhou, Tingtinga,*; Zhuang, Jingjingb,*; Wang, Zhiweia; Zhou, Yaodongc; Li, Wenc; Wang, Zhiminc; Zhu, Zhiyuanc

doi: 10.1097/WNR.0000000000001202
CELLULAR, MOLECULAR AND DEVELOPMENTAL NEUROSCIENCE
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Alzheimer’s disease (AD) is a progressive neurodegenerative disorder correlated with age, characterized by the accumulation of amyloid β (Aβ) plaques and neurofibrillary tangles. The mammalian target of rapamycin (mTOR) is an important protein that regulates Aβ clearance and tau phosphorylation. Therefore, mTOR has become a pivotal therapeutic target for AD treatment. In this study, we discovered a natural product, glaucocalyxin A (GLA), as a new mTOR inhibitor based on a high-throughput screening platform with α-screen technology against our natural product library. Further study showed that GLA increased Aβ clearance involving the protein kinase B/mTOR/autophagy signaling pathway and inhibited tau phosphorylation involving the mTOR/70-kDa ribosomal protein S6 kinase pathway, which highlighted the therapeutic potential of GLA for the AD treatment.

aWuxi School of Medicine, Jiangnan University, Wuxi

bMarine College, Shandong University, Weihai

cCentral Laboratory, Suzhou Kowloon Hospital, Shanghai Jiaotong University School of Medicine, Suzhou, China

*Tingting Zhoua and Jingjing Zhuang contributed equally to the writing of this article.

Correspondence to Zhiyuan Zhu, PhD, Central laboratory, Suzhou Kowloon Hospital, Shanghai Jiaotong University School of Medicine, 118 Wansheng Street, Suzhou 215028, China Tel: +86 126 262 7975; e-mail: zzysimm@aliyun.com

Received October 17, 2018

Accepted January 10, 2019

© 2019 Wolters Kluwer Health | Lippincott Williams & Wilkins