PMID- 31421130
OWN - NLM
STAT- MEDLINE
DCOM- 20201027
LR  - 20211204
IS  - 1872-6240 (Electronic)
IS  - 0006-8993 (Linking)
VI  - 1723
DP  - 2019 Nov 15
TI  - Neuroprotection by nicotinamide mononucleotide adenylyltransferase 1 with 
      involvement of autophagy in an aged rat model of transient cerebral ischemia and 
      reperfusion.
PG  - 146391
LID - S0006-8993(19)30445-7 [pii]
LID - 10.1016/j.brainres.2019.146391 [doi]
AB  - Recent researches suggest that autophagic degradation declines with age, and this 
      leads to an accumulation of damage that contributes to age-related cellular 
      dysfunction. Nicotinamide mononucleotide adenylyltransferase 1 (NMNAT1) shows 
      therapeutic potential for cerebral ischemia in young-adult animals. This study 
      investigated the role of NMNAT1 in focal cerebral ischemia in aged rats with a 
      focus on neuronal autophagy. Focal cerebral ischemia was induced in aged rats by 
      middle cerebral artery occlusion (MCAO). NMNAT1 levels in the peri-infarct 
      penumbra increased at 12 and 24 h after ischemia in aged rats. Knockdown of 
      NMNAT1 significantly increased infarct volume, whereas overexpression of NMNAT1 
      reduced ischemia-induced cerebral injuries in aged rats with acute ischemic 
      stroke. Meanwhile, lentiviral overexpression of NMNAT1 increased autophagy, 
      reduced the phosphorylation of mammalian target of rapamycin (mTOR), and enhanced 
      the sirtuin 1 (SIRT1) protein level. In cultured cortical neurons, SIRT1 
      regulated the mTOR-mediated autophagy upon oxygen-glucose deprivation (OGD) 
      stress and the effect of NMNAT1 on autophagy was blocked in cultured 
      SIRT1-knockout neurons. Furthermore, autophagy inhibitor 3-methyladenine (3-MA) 
      partly abolished the neuroprotection induced by NMNAT1 overexpression. The 
      results suggest NMNAT1 protects against acute ischemic stroke in aged rats by 
      inducing autophagy via regulating the SIRT1/mTOR pathway.
CI  - Copyright (c) 2019 Elsevier B.V. All rights reserved.
FAU - Wang, Peng
AU  - Wang P
AD  - Liaoning Key Laboratory of Neurodegenerative Diseases and Department of 
      Neurobiology, Jinzhou Medical University, Jinzhou, Liaoning, China.
FAU - Lu, Yijun
AU  - Lu Y
AD  - Department of Anesthesiology, The First Affiliated Hospital of Jinzhou Medical 
      University, Jinzhou, Liaoning, China.
FAU - Han, Donghe
AU  - Han D
AD  - Liaoning Key Laboratory of Neurodegenerative Diseases and Department of 
      Neurobiology, Jinzhou Medical University, Jinzhou, Liaoning, China.
FAU - Wang, Pan
AU  - Wang P
AD  - Liaoning Key Laboratory of Neurodegenerative Diseases and Department of 
      Neurobiology, Jinzhou Medical University, Jinzhou, Liaoning, China.
FAU - Ren, Lili
AU  - Ren L
AD  - Liaoning Key Laboratory of Neurodegenerative Diseases and Department of 
      Neurobiology, Jinzhou Medical University, Jinzhou, Liaoning, China.
FAU - Bi, Jing
AU  - Bi J
AD  - Liaoning Key Laboratory of Neurodegenerative Diseases and Department of 
      Neurobiology, Jinzhou Medical University, Jinzhou, Liaoning, China.
FAU - Liang, Jia
AU  - Liang J
AD  - Institute of Life Science, Jinzhou Medical University, Jinzhou, Liaoning, China. 
      Electronic address: liangjia8123@126.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190814
PL  - Netherlands
TA  - Brain Res
JT  - Brain research
JID - 0045503
RN  - 0 (Neuroprotective Agents)
RN  - 5142-23-4 (3-methyladenine)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.7.1 (NMNAT1 protein, rat)
RN  - EC 2.7.7.1 (Nicotinamide-Nucleotide Adenylyltransferase)
RN  - EC 3.5.1.- (Sirtuin 1)
RN  - IY9XDZ35W2 (Glucose)
RN  - JAC85A2161 (Adenine)
RN  - S88TT14065 (Oxygen)
SB  - IM
MH  - Adenine/analogs & derivatives/metabolism
MH  - Animals
MH  - Autophagy/*drug effects
MH  - Brain Ischemia/*drug therapy
MH  - Glucose/metabolism
MH  - Infarction, Middle Cerebral Artery/drug therapy
MH  - Ischemic Attack, Transient/metabolism
MH  - Male
MH  - Neurons/metabolism
MH  - Neuroprotection/drug effects
MH  - Neuroprotective Agents/pharmacology
MH  - Nicotinamide-Nucleotide Adenylyltransferase/genetics/*metabolism/pharmacology
MH  - Oxygen/metabolism
MH  - Rats
MH  - Reperfusion
MH  - Reperfusion Injury/metabolism
MH  - Signal Transduction/drug effects
MH  - Sirtuin 1/metabolism
MH  - Stroke/drug therapy/metabolism
MH  - TOR Serine-Threonine Kinases/metabolism
OTO - NOTNLM
OT  - Autophagy
OT  - Ischemic stroke
OT  - NMNAT1
OT  - Neuroprotection
EDAT- 2019/08/20 06:00
MHDA- 2020/10/28 06:00
CRDT- 2019/08/18 06:00
PHST- 2019/05/16 00:00 [received]
PHST- 2019/07/20 00:00 [revised]
PHST- 2019/08/13 00:00 [accepted]
PHST- 2019/08/20 06:00 [pubmed]
PHST- 2020/10/28 06:00 [medline]
PHST- 2019/08/18 06:00 [entrez]
AID - S0006-8993(19)30445-7 [pii]
AID - 10.1016/j.brainres.2019.146391 [doi]
PST - ppublish
SO  - Brain Res. 2019 Nov 15;1723:146391. doi: 10.1016/j.brainres.2019.146391. Epub 
      2019 Aug 14.