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  • Melatonin receptor stimulation by agomelatine prevents Aβ-induced tau phosphorylation and oxidative damage in PC12 cells.

Melatonin receptor stimulation by agomelatine prevents Aβ-induced tau phosphorylation and oxidative damage in PC12 cells.

Drug design, development and therapy (2019-02-06)
Kai Yao, Yong-Fei Zhao, Heng-Bing Zu
ABSTRACT

As a novel antidepressant drug, agomelatine has good therapeutic effect on the mood disorder and insomnia in Alzheimer's disease (AD). Recent studies have shown the neuroprotective function of agomelatine, including anti-oxidative and anti-apoptosis effect. However, it remains unclear whether agomelatine exerts neuroprotection in AD. Thus, the neuroprotective effect of agomelatine against amyloid beta 25-35 (Aβ25-35)-induced toxicity in PC12 cells was evaluated in this study. The concentration of malondialdehyde (MDA), LDH, and ROS was investigated to evaluate oxidative damage. The expression of P-tau, tau, PTEN, P-Akt, Akt, P-GSK3β, and GSK3β proteins was assessed by Western blotting. Our results demonstrated that Aβ25-35 significantly increased the content of MDA, LDH, and ROS. Meanwhile, Aβ25-35 upregulated the expression of P-tau and PTEN as well as downregulated P-Akt and P-GSK3β expression. These effects could be blocked by agomelatine pretreatment. Furthermore, luzindole, the melatonin receptor (MT) antagonist, could reverse the neuroprotective effect of agomelatine. The results demonstrated that antidepressant agomelatine might prevent the tau protein phosphorylation and oxidative damage induced by Aβ25-35 in PC12 cells by activating MT-PTEN/Akt/GSK3β signaling. This study provided a novel therapeutic target for AD in the future.

MATERIALS
Product Number
Brand
Product Description

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