AffiliationUniv Arizona, Coll Sci
MetadataShow full item record
PublisherIMPACT JOURNALS LLC
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.101592
RightsCopyright © Yin et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0).
Collection InformationThis 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 email@example.com.
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.
NoteOpen access journal
VersionFinal published version
SponsorsNational Institute on Aging [P30 AG19610]; Arizona Department of Health Services ; Barrow Neurological Foundation ; National Science Foundation of China 
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).
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