Aβ25–35 Suppresses Mitochondrial Biogenesis in Primary Hippocampal Neurons
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  • 作者:Weiguo Dong ; Feng Wang ; Wanqing Guo ; Xuehua Zheng…
  • 关键词:Alzheimer’s disease ; Mitochondrial biogenesis ; Amyloid ; β ; AMPK ; SIRT1 ; PGC ;
  • 刊名:Cellular and Molecular Neurobiology
  • 出版年:2016
  • 出版时间:January 2016
  • 年:2016
  • 卷:36
  • 期:1
  • 页码:83-91
  • 全文大小:865 KB
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  • 作者单位:Weiguo Dong (1)
    Feng Wang (1)
    Wanqing Guo (2)
    Xuehua Zheng (1)
    Yue Chen (1)
    Wenguang Zhang (1)
    Hong Shi (1)

    1. Department of Integrated Traditional Chinese and Western Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, Fujian, People’s Republic of China
    2. The Third People’s Hospital of Fujian Province, Fuzhou, 350122, Fujian, People’s Republic of China
  • 刊物类别:Biomedical and Life Sciences
  • 刊物主题:Biomedicine
    Neurosciences
    Animal Anatomy, Morphology and Histology
  • 出版者:Springer Netherlands
  • ISSN:1573-6830
文摘
Mitochondrial biogenesis is involved in the regulation of mitochondrial content, morphology, and function. Impaired mitochondrial biogenesis has been observed in Alzheimer’s disease. Amyloid-β (Aβ) has been shown to cause mitochondrial dysfunction in cultured neurons, but its role in mitochondrial biogenesis in neurons remains poorly defined. AMP-activated protein kinase (AMPK) and sirtuin 1 (SIRT1) are key energy-sensing molecules regulating mitochondrial biogenesis. In addition, peroxisome proliferator-activated receptor-γ coactivator 1-alpha (PGC-), the master regulator of mitochondrial biogenesis, is a target for SIRT1 deacetylase activity. In this study, we investigated the effects of Aβ25–35 on mitochondrial biogenesis in cultured hippocampal neurons and the underlying mechanisms. In primary hippocampal neurons, we found that 24-h incubation with Aβ25–35 suppressed both phosphorylations of AMPK and SIRT1 expression and increased PGC- acetylation expression. In addition, Aβ25–35 also resulted in a decrease in mitochondrial DNA copy number, as well as decreases in the expression of mitochondrial biogenesis factors (PGC-, NRF 1, NRF 2, and Tfam). Taken together, these data show that Aβ25–35 suppresses mitochondrial biogenesis in hippocampal neurons. Aβ25–35-induced impairment of mitochondrial biogenesis may be associated with the inhibition of the AMPK-SIRT1-PGC- pathway. Keywords Alzheimer’s disease Mitochondrial biogenesis Amyloid-β AMPK SIRT1 PGC-

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