Data Management And Sharing System of China National Clinical Research Center for Neurological Diseases
Sirtuin 3 attenuates amyloid-β induced neuronal hypometabolism
First author：Yin Junxiang,Li Shiping
Corresponding author：Shi Jiong
essential_information
- Person in charge：Yin Junxiang,Li Shiping
- Data Sources： OTHERS
- Number of papers：OTHERS20190624
- Published time：2018-10-23
2018-10-23
Published articles
Journal：Aging
Publication type: Article
IF(IF): 5.515
PMID: 30362958 Link To Pubmed Full text Download
Background And Purpose
Method
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.
Conclusion
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.
Main results
In APP mice, the NAD+ level, NAD+/ NADH ratio, Sirt3 protein level and activity, and ATP production were all reduced compared to the control.