标题：Melatonin protects against A-induced neurotoxicity in primary neurons via miR-132/PTEN/AKT/FOXO3a pathway
作者：Zhao, Yue; Zhao, Ranran; Wu, Jintao; Wang, Qian; Pang, Kunkun; Shi, Qingqing; Gao, Qing; Hu, Yanlai; Dong, Xiaoguang; Zhang, Jing; 更多 作者机构：[Zhao, Yue; Wu, Jintao; Wang, Qian; Pang, Kunkun; Shi, Qingqing; Hu, Yanlai; Zhang, Jing; Sun, Jinhao] Shandong Univ, Sch Basic Med, Dept Anat, Jinan 更多
通讯作者地址：[Sun, JH]Shandong Univ, Sch Med, Dept Anat, 44 Wenhua Xi Rd, Jinan 250012, Shandong, Peoples R China.
关键词：amyliod-; melatonin; neurotoxicity; miR-132
摘要：Alzheimer's disease (AD) is a kind of neurodegenerative disorder associated with age. Investigations suggest that amyliod- (A) is implicated in the pathogenesis of AD. The accumulation of A in the brain causes oxidative stress and synaptic toxicity, leads to synaptic dysfunction and neuronal death. Previous investigations suggest that melatonin an endogenous hormone can counteract A-induced neurotoxicity. However, the molecular mechanisms of A-induced toxicity and melatonin treatment remain elusive. Studies indicate that microRNA-132 is crucial for neuronal survival and plays a key role in the pathological process of AD. Moreover, PTEN and FOXO3a two key targets of miR-132 are upregulated in the AD brain. Here, we exposed the primary cultured cortical neurons with A25-35 and treated with melatonin. Our investigations demonstrated that A25-35 exposure significantly decreased the expression of miR-132 and elevated the expression of PTEN and FOXO3a. Whereas, melatonin treatment could rescue the expression of miR-132 and downregulate the level of PTEN and FOXO3a. Moreover, melatonin blocked the nuclear translocation of FOXO3a and thereby suppressed its pro-apoptotic pathways. In addition, our investigations suggested that the over-expression of miR-132 could block A-induced neurotoxicity. We also found that VO-OHpic (PTEN inhibitor) could counteract A-induced neuronal damage, and LY294002 (AKT inhibitor) suppressed the protective effect of melatonin. Together, these results indicate that melatonin exerts its neuroprotective effect in A-induced neurotoxicity via miR-132/PTEN/AKT/FOXO3a pathway. (c) 2018 BioFactors, 44(6):609-618, 2018