机构：[1]School of Life Sciences, Huizhou University, 46 Yanda Avenue, Huizhou 516007, Guangdong, People’s Republic of China[2]Department of Neurology, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, Heilongjiang, People’s Republic of China[3]Department of Obstetrics and Gynecology, Huizhou Third People’s Hospital, Huizhou, Huizhou 516002, Guangdong, People’s Republic of China[4]Department of Neurology, Huizhou Third People’s Hospital, Huizhou 516002, Guangdong, People’s Republic of China[5]Department of ChineseMedicine, Dalian Maternity and Child Health Care Hospital, Dalian 116033, Liaoning, People’s Republic of China
Autophagy, a lysosomal degradative pathway, is crucial for the pathogenesis of Alzheimer's disease (AD). Schizandrol A (SchA) shows multiple pharmacological effects. However, the potential effects and mechanisms of SchA on amyloid-β (Aβ)-induced autophagy remain unclear. In this study, differentiated SH-SY5Y cells or primary hippocampal neurons were pretreated with SchA (2 μg/ml) for 1 h before subjected to Aβ1-42 (10 μM) for 24 h to test its effects on cell viability, apoptosis, oxidative stress, and autophagy. Then an mTOR inhibitor (rapamycin) and a PI3K inhibitor (LY294002) were employed to explore the role of PI3K/AKT/mTOR pathway. The results showed that SchA significantly inhibited Aβ1-42-triggered reduction of viable cells, increases of apoptotic cell number and pro-apoptotic protein expressions, as well as alterations of oxidative stress markers. In addition, the increases of LC3-II/LC3-I and Beclin-1 and decrease of p62 were suppressed by SchA. At the molecular level, we found that the inactivation of PI3K/AKT/mTOR pathway was ameliorated by SchA. Inhibition of PI3K/AKT/mTOR pathway deteriorated the protective effects of SchA against Aβ1-42-induced autophagy activation, cell death, and apoptosis. In conclusion, we demonstrate that SchA attenuates Aβ1-42-induced autophagy through activating PI3K/AKT/mTOR signaling pathway. SchA may be a novel drug for the prevention and treatment of AD.
基金：
the
National Natural Science Foundation of China (No. 81271208) and the
Scientific Research Project of Heilongjiang Provincial Health and Family
Planning Commission (No. 2017-501).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2019]版：
大类|4 区医学
小类|4 区药学
最新[2025]版：
大类|4 区医学
小类|4 区药学
第一作者：
第一作者机构：[1]School of Life Sciences, Huizhou University, 46 Yanda Avenue, Huizhou 516007, Guangdong, People’s Republic of China
通讯作者：
推荐引用方式(GB/T 7714)：
Song Lin,Yao Lifen,Zhang Limei,et al.Schizandrol A protects against Aβ1-42-induced autophagy via activation of PI3K/AKT/mTOR pathway in SH-SY5Y cells and primary hippocampal neurons.[J].Naunyn-Schmiedeberg's archives of pharmacology.2020,393(9):1739-1752.doi:10.1007/s00210-019-01792-2.
APA：
Song Lin,Yao Lifen,Zhang Limei,Piao Zhongyuan&Lu Yichan.(2020).Schizandrol A protects against Aβ1-42-induced autophagy via activation of PI3K/AKT/mTOR pathway in SH-SY5Y cells and primary hippocampal neurons..Naunyn-Schmiedeberg's archives of pharmacology,393,(9)
MLA：
Song Lin,et al."Schizandrol A protects against Aβ1-42-induced autophagy via activation of PI3K/AKT/mTOR pathway in SH-SY5Y cells and primary hippocampal neurons.".Naunyn-Schmiedeberg's archives of pharmacology 393..9(2020):1739-1752
