title: Nicotinamide Mononucleotide Adenylyltransferase 1 Protects Neural Cells Against Ischemic Injury in Primary Cultured Neuronal Cells and Mouse Brain with Ischemic Stroke Through AMP-Activated Protein Kinase Activation.
abstract: Nicotinamide mononucleotide adenylyltransferase 1 (NMNAT1) is a nicotinamide adenine dinucleotide biosynthetic enzyme. It has been shown to be neuroprotective against neonatal excitotoxicity-induced brain injury, but its role in ischemic stroke is unclear. In this study, the role of NMNAT1 in oxygen-glucose deprivation (OGD)-induced primary cultured neuronal cell injury and mouse middle cerebral artery occlusion-induced cerebral ischemic injury and its regulation on AMP-activated protein kinase (AMPK) activation were evaluated. The results showed that NMNAT1 overexpression reduced cell death and apoptosis both in vitro and in vivo. Conversely, NMNAT1 knockdown exacerbated cell death and apoptosis. Furthermore, NMNAT1 overexpression regulated neuron survival via AMPK activation, as NMNAT1 overexpression enhanced AMPK activity in OGD-treated cortical neurons, and AMPK inhibitor blocked LV-NMNAT1-induced neuroprotection in OGD-treated cortical neurons. In addition, NMNAT1 overexpression could reduce brain infarction size and improve behavioral outcomes in mice with ischemic stroke. These results suggested that up-regulation of NMNAT1 could induce neuroprotection against ischemic injury through AMPK activation and indicated that NMNAT1 is a potential therapeutic target for stroke.
authors.affiliation: Key Laboratory of Molecular Cell Biology and New Drug Development, Liaoning Medical University, Jinzhou, 121001, People's Republic of China.
authors.forename: Jia
authors.initials: J
authors.lastname: Liang
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
authors.forename: Jia
authors.initials: J
authors.lastname: Wei
authors.forename: Cuifen
authors.initials: C
authors.lastname: Bao
authors.forename: Donghe
authors.initials: D
authors.lastname: Han
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001522:Behavior, Animal; D001921:Brain / Q000473:pathology*; D002545:Brain Ischemia / Q000473:pathology* / Q000523:psychology; D002544:Cerebral Infarction / Q000473:pathology; D004789:Enzyme Activation / Q000235:genetics; D005947:Glucose / Q000172:deficiency; D002534:Hypoxia, Brain / Q000473:pathology; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000473:pathology*; D009612:Nicotinamide-Nucleotide Adenylyltransferase / Q000096:biosynthesis / Q000235:genetics*; D061251:Primary Cell Culture; D020521:Stroke / Q000473:pathology* / Q000523:psychology
chemical_list: D055372:AMP-Activated Protein Kinases; D009612:Nicotinamide-Nucleotide Adenylyltransferase; C510972:Nmnat1 protein, mouse; D005947:Glucose
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