Schizandrol A protects against Aβ1–42-induced autophagy via activation of PI3K/AKT/mTOR pathway in SH-SY5Y cells and primary hippocampal neurons

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Abstract
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.
Funding Information
  • National Natural Science Foundation of China (No.81271208)
  • Scientific Research Project of Heilongjiang Provincial Health and Family Planning Commission (No. 2017-501)

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