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dc.contributor.authorYin, Junxiang
dc.contributor.authorLi, Shiping
dc.contributor.authorNielsen, Megan
dc.contributor.authorCarcione, Tanner
dc.contributor.authorLiang, Winnie S
dc.contributor.authorShi, Jiong
dc.date.accessioned2019-05-22T18:59:25Z
dc.date.available2019-05-22T18:59:25Z
dc.date.issued2018-10-23
dc.identifier.citationYin J, Li S, Nielsen M, Carcione T, Liang WS, Shi J. Sirtuin 3 attenuates amyloid-β induced neuronal hypometabolism. Aging (Albany NY). 2018; 10:2874-2883. https://doi.org/10.18632/aging.101592en_US
dc.identifier.issn1945-4589
dc.identifier.pmid30362958
dc.identifier.doi10.18632/aging.101592
dc.identifier.urihttp://hdl.handle.net/10150/632368
dc.description.abstractAlzheimer's disease (AD) is manifested by regional cerebral hypometabolism. Sirtuin 3 (Sirt3) is localized in mitochondria and regulates cellular metabolism, but the role of Sirt3 in AD-related hypometabolism remains elusive. We used expression profiling and weighted gene co-expression network analysis (WGCNA) to analyze cortical neurons from a transgenic mouse model of AD (APPSwInd). Based on WGCNA results, we measured NAD+ level, NAD+/ NADH ratio, Sirt3 protein level and its deacetylation activity, and ATP production across both in vivo and in vitro models. To investigate the effect of Sirt3 on amyloid-β (Aβ)-induced mitochondria damage, we knocked down and over-expressed Sirt3 in hippocampal cells. WGCNA revealed Sirt3 as a key player in Aβ-related hypometabolism. In APP mice, the NAD+ level, NAD+/ NADH ratio, Sirt3 protein level and activity, and ATP production were all reduced compared to the control. As a result, learning and memory performance were impaired in 9-month-old APP mice compared to wild type controls. Using hippocampal HT22 cells model, Sirt3 overexpression increased Sirt3 deacetylation activity, rescued mitochondria function, and salvaged ATP production, which were damaged by Aβ. Sirt3 plays an important role in regulating Aβ-induced cerebral hypometabolism. This study suggests a potential direction for AD therapy.en_US
dc.description.sponsorshipNational Institute on Aging [P30 AG19610]; Arizona Department of Health Services [211002]; Barrow Neurological Foundation [3032226]; National Science Foundation of China [81671050]en_US
dc.language.isoenen_US
dc.publisherIMPACT JOURNALS LLCen_US
dc.relation.urlhttps://www.aging-us.com/article/101592/texten_US
dc.rightsCopyright © Yin et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0).en_US
dc.rights.urihttps://creativecommons.org/licenses/by/3.0/
dc.subjectAlzheimer’s diseaseen_US
dc.subjectSirtuin 3en_US
dc.subjectamyloiden_US
dc.subjectcerebral hypometabolismen_US
dc.titleSirtuin 3 attenuates amyloid-β induced neuronal hypometabolismen_US
dc.typeArticleen_US
dc.contributor.departmentUniv Arizona, Coll Scien_US
dc.identifier.journalAGING-USen_US
dc.description.noteOpen access journalen_US
dc.description.collectioninformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.en_US
dc.eprint.versionFinal published versionen_US
dc.source.journaltitleAging
refterms.dateFOA2019-05-22T18:59:26Z


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Copyright © Yin et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0).
Except where otherwise noted, this item's license is described as Copyright © Yin et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0).