标题：Glaucocalyxin A as a natural product increases amyloid beta clearance and decreases tau phosphorylation involving the mammalian target of rapamycin signaling pathway
作者：Zhou, Tingting; Zhuang, Jingjing; Wang, Zhiwei; Zhou, Yaodong; Li, Wen; Wang, Zhimin; Zhu, Zhiyuan
作者机构：[Zhou, Tingting; Wang, Zhiwei] Jiangnan Univ, Wuxi Sch Med, Wuxi, Peoples R China.; [Zhuang, Jingjing] Shandong Univ, Marine Coll, Weihai, Peoples R 更多
通讯作者地址：[Zhu, ZY]Shanghai Jiao Tong Univ, Suzhou Kowloon Hosp, Sch Med, Cent Lab, 118 Wansheng St, Suzhou 215028, Peoples R China.
关键词：Alzheimer's disease; autophagy; amyloid beta; glaucocalyxin A; mammalian; target of rapamycin; tau
摘要：Alzheimer's disease (AD) is a progressive neurodegenerative disorder correlated with age, characterized by the accumulation of amyloid beta (A beta) plaques and neurofibrillary tangles. The mammalian target of rapamycin (mTOR) is an important protein that regulates A beta 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 alpha-screen technology against our natural product library. Further study showed that GLA increased A beta 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.