Pretreatment with metformin prevents microcystin-LR-induced tau hyperphosphorylation via mTOR-dependent PP2A and GSK-3β activation.
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| Abstract |
Microcystin-leucine-arginine (MC-LR) is a toxin secreted by freshwater cyanobacteria that is considered a potential environmental risk factor for Alzheimer's disease (AD). A previous study indicated that tau protein hyperphosphorylation via protein phosphatase 2A (PP2A) and GSK-3β inhibition was the mechanism by which MC-LR induces neurotoxicity; however, how MC-LR-induced neurotoxicity can be effectively prevented remains unclear. In this study, the reversal effect of metformin on MC-LR-induced neurotoxicity was investigated. The results showed that metformin effectively prevented tau hyperphosphorylation at Ser202 caused by MC-LR through PP2A and GSK-3b activity. The effect of metformin on PP2A activity was dependent on the inhibition of mTOR in MC-LR-treated SH-SY5Y cells. Metformin prevented spatial memory deficits in rats caused by intrahippocampal MC-LR administration. In sum, the results suggested that metformin can ameliorate the MC-LR-induced AD-like phenotype by preventing tau phosphorylation at Ser202, which was mainly mediated by mTOR-dependent PP2A and GSK-3β activation.
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| Authors | Yali Zhang, Xing Fan, Zhangyao Su, Tianli Yuan, Haimeng Yin, Haohao Gu, Yue Zuo, Shiyin Chen, Hongyu Zhou, Gaoxing Su |
| Journal | Environmental toxicology (Environ Toxicol) Vol. 36 Issue 12 Pg. 2414-2425 (Dec 2021) ISSN: 1522-7278 [Electronic] United States |
| PMID | 34432352 (Publication Type: Journal Article) |
| Copyright | © 2021 Wiley Periodicals LLC. |
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