PMID- 28099881
OWN - NLM
STAT- MEDLINE
DCOM- 20171026
LR  - 20211204
IS  - 1873-6815 (Electronic)
IS  - 0531-5565 (Linking)
VI  - 89
DP  - 2017 Mar
TI  - Mesencephalic astrocyte-derived neurotrophic factor alleviated 6-OHDA-induced 
      cell damage via ROS-AMPK/mTOR mediated autophagic inhibition.
PG  - 45-56
LID - S0531-5565(16)30557-5 [pii]
LID - 10.1016/j.exger.2017.01.010 [doi]
AB  - 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.
CI  - Copyright (c) 2017 Elsevier Inc. All rights reserved.
FAU - Zhang, Jingxing
AU  - Zhang J
AD  - Department of Neurology, Shanghai Tongji Hospital, Tongji University School of 
      Medicine, 389 Xincun Road, Shanghai 200065, PR China.
FAU - Cai, Qiong
AU  - Cai Q
AD  - Department of Neurology, Shanghai Tongji Hospital, Tongji University School of 
      Medicine, 389 Xincun Road, Shanghai 200065, PR China.
FAU - Jiang, Ming
AU  - Jiang M
AD  - Biomedical Research Center, Tongji University Suzhou Institute, Building 2,198 
      Jinfeng Road, Wuzhong District, Suzhou, Jiangsu 215101, PR China.
FAU - Liu, Yigang
AU  - Liu Y
AD  - Department of Neurology, Shanghai Tongji Hospital, Tongji University School of 
      Medicine, 389 Xincun Road, Shanghai 200065, PR China.
FAU - Gu, Hua
AU  - Gu H
AD  - School of Life Science and Technology, Tongji University, 1239 Siping Road, 
      Shanghai 200092, PR China.
FAU - Guo, Jia
AU  - Guo J
AD  - Biomedical Research Center, Tongji University Suzhou Institute, Building 2,198 
      Jinfeng Road, Wuzhong District, Suzhou, Jiangsu 215101, PR China.
FAU - Sun, Hui
AU  - Sun H
AD  - Department of Neurology, Shanghai Tongji Hospital, Tongji University School of 
      Medicine, 389 Xincun Road, Shanghai 200065, PR China.
FAU - Fang, Jianmin
AU  - Fang J
AD  - 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.
FAU - Jin, Lingjing
AU  - Jin L
AD  - Department of Neurology, Shanghai Tongji Hospital, Tongji University School of 
      Medicine, 389 Xincun Road, Shanghai 200065, PR China. Electronic address: 
      lingjingjin@hotmail.com.
LA  - eng
PT  - Journal Article
DEP - 20170115
PL  - England
TA  - Exp Gerontol
JT  - Experimental gerontology
JID - 0047061
RN  - 0 (MANF protein, human)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Reactive Oxygen Species)
RN  - 8HW4YBZ748 (Oxidopamine)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
SB  - IM
MH  - AMP-Activated Protein Kinases/*metabolism
MH  - Apoptosis/drug effects
MH  - Autophagy/*drug effects
MH  - Cell Line, Tumor
MH  - Cell Survival/drug effects
MH  - Dopaminergic Neurons/*drug effects
MH  - Humans
MH  - Nerve Growth Factors/*pharmacology
MH  - Neuroprotective Agents/*pharmacology
MH  - Oxidopamine/toxicity
MH  - Parkinson Disease/physiopathology
MH  - Reactive Oxygen Species/metabolism
MH  - Signal Transduction/drug effects
MH  - TOR Serine-Threonine Kinases/*metabolism
OTO - NOTNLM
OT  - Apoptosis
OT  - Autophagy
OT  - MANF
OT  - ROS
OT  - SH-SY5Y cells
EDAT- 2017/01/19 06:00
MHDA- 2017/10/27 06:00
CRDT- 2017/01/19 06:00
PHST- 2016/11/30 00:00 [received]
PHST- 2017/01/08 00:00 [revised]
PHST- 2017/01/13 00:00 [accepted]
PHST- 2017/01/19 06:00 [pubmed]
PHST- 2017/10/27 06:00 [medline]
PHST- 2017/01/19 06:00 [entrez]
AID - S0531-5565(16)30557-5 [pii]
AID - 10.1016/j.exger.2017.01.010 [doi]
PST - ppublish
SO  - Exp Gerontol. 2017 Mar;89:45-56. doi: 10.1016/j.exger.2017.01.010. Epub 2017 Jan 
      15.