国家神经系统疾病临床医学研究中心数据管理与共享系统

Data Management And Sharing System of China National Clinical Research Center for Neurological Diseases

《国家中心数据管理与共享系统操作说明书 —— 研究者部分》

Sirtuin 3 attenuates amyloid-β induced neuronal hypometabolism

第一作者：Yin Junxiang,Li Shiping

通讯作者：Shi Jiong

Sirtuin 3 Alzheimer’s disease cerebral hypometabo

基本信息

2018-10-23

已发表文章

发表杂志：Aging

发表类型: Article

影响因子(IF): 5.515

PMID: 30362958 Pubmed原文链接 全文下载

主要研究背景及目的

方法

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.

结论

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.

主要结果

In APP mice, the NAD+ level, NAD+/ NADH ratio, Sirt3 protein level and activity, and ATP production were all reduced compared to the control.