Jingxing Zhang, Qiong Cai, Ming Jiang, Yigang Liu, Hua Gu, Jia Guo, Hui Sun, Jianmin Fang, Lingjing Jin
Author Information
Jingxing Zhang: Department of Neurology, Shanghai Tongji Hospital, Tongji University School of Medicine, 389 Xincun Road, Shanghai 200065, PR China.
Qiong Cai: Department of Neurology, Shanghai Tongji Hospital, Tongji University School of Medicine, 389 Xincun Road, Shanghai 200065, PR China.
Ming Jiang: Biomedical Research Center, Tongji University Suzhou Institute, Building 2,198 Jinfeng Road, Wuzhong District, Suzhou, Jiangsu 215101, PR China.
Yigang Liu: Department of Neurology, Shanghai Tongji Hospital, Tongji University School of Medicine, 389 Xincun Road, Shanghai 200065, PR China.
Hua Gu: School of Life Science and Technology, Tongji University, 1239 Siping Road, Shanghai 200092, PR China.
Jia Guo: Biomedical Research Center, Tongji University Suzhou Institute, Building 2,198 Jinfeng Road, Wuzhong District, Suzhou, Jiangsu 215101, PR China.
Hui Sun: Department of Neurology, Shanghai Tongji Hospital, Tongji University School of Medicine, 389 Xincun Road, Shanghai 200065, PR China.
Jianmin Fang: School of Life Science and Technology, Tongji University, 1239 Siping Road, Shanghai 200092, PR China; Biomedical Research Center, Tongji University Suzhou Institute, Building 2,198 Jinfeng Road, Wuzhong District, Suzhou, Jiangsu 215101, PR China. Electronic address: jfang@tongji.edu.cn.
Lingjing Jin: Department of Neurology, Shanghai Tongji Hospital, Tongji University School of Medicine, 389 Xincun Road, Shanghai 200065, PR China. Electronic address: lingjingjin@hotmail.com.
Autophagy and apoptosis are commonly involved in the dopaminergic neuron damage in the pathogenesis of Parkinson's disease. Recently, the autophagy pathway is thought to be critical to the process of PD. Therefore, the regulation of autophagy may be a potential strategy for PD treatment. Mesencephalic astrocyte-derived neurotrophic factor (MANF) has been reported to have neuroprotective effects through anti-apoptosis, anti-oxidative, and anti-inflammatory mechanisms in PD. In this study, we investigated the role of autophagy system in MANF-mediated neuroprotection against 6-hydroxydopamine (6-OHDA)-induced neurotoxicity. Our results showed that MANF protected SH-SY5Y cells against 6-OHDA-induced cell viability decrease and apoptosis by inhibiting autophagy. Mitochondrion damage and energetic dysfunction triggered by reactive oxidative stress (ROS) accumulation were also alleviated by MANF treatment. Furthermore, MANF downregulated phosphorylation of AMP-activated protein kinase (AMPK), a cellular energy sensor and regulator, but upregulated phosphorylation of Mammalian target of rapamycin (mTOR) under energy depletion conditions, indicating AMPK/mTOR signaling pathway is involved in the autophagic inhibition of MANF. These results suggest that autophagic inhibition provides protective mechanism of MANF in 6-OHDA-induced SH-SY5Y cell death and this inhibition is associated with AMPK/mTOR pathway.
