Tags

Type your tag names separated by a space and hit enter

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.

Links

Publisher Full Text (DOI)

Authors+Show Affiliations

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

MeSH

Amyloid beta-PeptidesAnimalsApoptosisAutophagyAutophagy-Related ProteinsCell Line, TumorCyclooctanesDopaminergic NeuronsHippocampusHumansLignansNeuroprotective AgentsOxidative StressPeptide FragmentsPhosphatidylinositol 3-KinasePhosphorylationPolycyclic CompoundsPrimary Cell CultureProto-Oncogene Proteins c-aktRatsSignal TransductionTOR Serine-Threonine Kinasestau Proteins

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_ DB - PRIME DP - Unbound Medicine ER -