期刊
NEUROCHEMICAL RESEARCH
卷 41, 期 9, 页码 2311-2323出版社
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s11064-016-1945-6
关键词
Carnosic acid; Alzheimer's disease; Neuroprotection; Autophagy; AMP-activated protein kinase
Beta-amyloid (A beta), the hallmark protein in Alzheimer's disease (AD), induces neurotoxicity that involves oxidative stress and mitochondrial dysfunction, leading to cell death. Carnosic acid (CA), a polyphenolic diterpene isolated from the herb rosemary (Rosemarinus officinalis), was investigated in our study to assess its neuroprotective effect and underlying mechanism against A beta-induced injury in human neuroblastoma SH-SY5Y cells. We found that CA pretreatment alleviated the A beta(25-35)-induced loss of cell viability, inhibited both A beta(1-42) accumulation and tau hyperphosphorylation, reduced reactive oxygen species generation, and maintained the mitochondrial membrane potential. Moreover, CA increased the microtubule-associated protein light chain 3 (LC3)-II/I ratio and decreased SQSTM1(p62), indicating that CA could induce autophagy. Autophagy inhibitor 3-methyladenine (3-MA) attenuated the neuroprotective effect of CA, suggesting that autophagy was involved in the neuroprotection of CA. It was also observed that CA activated AMP-activated protein kinase (AMPK) but inhibited mammalian target of rapamycin (mTOR). Furthermore, blocking AMPK with si-AMPK alpha successfully inhibited the upregulation of LC3-II/I, prevented the downregulation of phosphorylation of mTOR and SQSTM1(p62), indicating that CA induced autophagy in SH-SY5Y cells via the activation of AMPK. These results suggested that CA might be a potential agent for preventing AD.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据