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Neuroprotective effects of olanzapine against rotenone-induced toxicity in PC12 cells

  
@article{APS10122,
	author = {Ya-jie Xiong and Yun-zhen Song and Ying Zhu and Wen-qing Zuo and Yi-fan Zhao and Xiao Shen and Wen-juan Wang and Ya-li Liu and Jun-chao Wu and Zhong-qin Liang},
	title = {Neuroprotective effects of olanzapine against rotenone-induced toxicity in PC12 cells},
	journal = {Acta Pharmacologica Sinica},
	volume = {41},
	number = {4},
	year = {2020},
	keywords = {},
	abstract = {Olanzapine is an antipsychotic drug used to treat patients with schizophrenia due to its lower incidence of extrapyramidal symptoms. Previous studies have shown that olanzapine activates AMP-activated protein kinase (AMPK), and induce autophagy in SH-SY5Y cell line. In this study, we investigated whether olanzapine protected against rotenone-induced neurotoxicity in PC12 cells. We showed that treatment with olanzapine increased the phosphorylation of AMPK in both dose- and time-dependent manners in PC12 cells. In addition, olanzapine activated autophagy and increased autophagic vacuoles. Furthermore, olanzapine pretreatment could protect PC12 cells from rotenone-induced apoptosis. Besides, olanzapine pretreatment could suppress the rotenone-induced depolarization of mitochondrial potential and thus protect the cells. Moreover, pretreatment with specific AMPK inhibitor compound C or with autophagy inhibitor 3-methyladenine impaired the protective effect of olanzapine on rotenone-treated PC12 cells. In summary, our results show for the first time that olanzapine ameliorates rotenone-induced injury by activating autophagy through AMPK pathway.},
	issn = {1745-7254},	url = {http://www.chinaphar.com/article/view/10122}
}