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Schizandrol A protects against Aβ1-42-induced autophagy via activation of PI3K/AKT/mTOR pathway in SH-SY5Y cells and primary hippocampal neurons.
Naunyn Schmiedebergs Arch Pharmacol. 2020 09; 393(9):1739-1752.NS

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.

Authors+Show Affiliations

School of Life Sciences, Huizhou University, 46 Yanda Avenue, Huizhou, 516007, Guangdong, People's Republic of China. drlinsong@163.com.Department of Neurology, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, Heilongjiang, People's Republic of China.Department of Obstetrics and Gynecology, Huizhou Third People's Hospital, Huizhou, Huizhou, 516002, Guangdong, People's Republic of China.Department of Neurology, Huizhou Third People's Hospital, Huizhou, 516002, Guangdong, People's Republic of China.Department of Chinese Medicine, Dalian Maternity and Child Health Care Hospital, Dalian, 116033, Liaoning, People's Republic of China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31900522

Citation

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, vol. 393, no. 9, 2020, pp. 1739-1752.
Song L, Yao L, Zhang L, 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 Schmiedebergs Arch Pharmacol. 2020;393(9):1739-1752.
Song, L., Yao, L., Zhang, L., Piao, Z., & Lu, Y. (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), 1739-1752. https://doi.org/10.1007/s00210-019-01792-2
Song L, 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 Schmiedebergs Arch Pharmacol. 2020;393(9):1739-1752. PubMed PMID: 31900522.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Schizandrol A protects against Aβ1-42-induced autophagy via activation of PI3K/AKT/mTOR pathway in SH-SY5Y cells and primary hippocampal neurons. AU - Song,Lin, AU - Yao,Lifen, AU - Zhang,Limei, AU - Piao,Zhongyuan, AU - Lu,Yichan, Y1 - 2020/01/04/ PY - 2019/04/30/received PY - 2019/12/05/accepted PY - 2020/1/5/pubmed PY - 2021/7/29/medline PY - 2020/1/5/entrez KW - Autophagy KW - Aβ1–42 KW - PI3K/AKT/mTOR pathway KW - Schizandrol A SP - 1739 EP - 1752 JF - Naunyn-Schmiedeberg's archives of pharmacology JO - Naunyn Schmiedebergs Arch Pharmacol VL - 393 IS - 9 N2 - 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. SN - 1432-1912 UR - https://www.unboundmedicine.com/medline/citation/31900522/Schizandrol_A_protects_against_Aβ1_42_induced_autophagy_via_activation_of_PI3K/AKT/mTOR_pathway_in_SH_SY5Y_cells_and_primary_hippocampal_neurons_ L2 - https://dx.doi.org/10.1007/s00210-019-01792-2 DB - PRIME DP - Unbound Medicine ER -