In:
Environmental Toxicology, Wiley, Vol. 36, No. 12 ( 2021-12), p. 2414-2425
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.
Type of Medium:
Online Resource
ISSN:
1520-4081
,
1522-7278
Language:
English
Publisher:
Wiley
Publication Date:
2021
detail.hit.zdb_id:
2027534-1
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