Aβ25–35 Suppresses Mitochondrial Biogenesis in Primary Hippocampal Neurons
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-1α), 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-1α 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-1α, 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-1α pathway.
KeywordsAlzheimer’s disease Mitochondrial biogenesis Amyloid-β AMPK SIRT1 PGC-1α
This work was supported by the National Natural Science Foundation of China (Project 81102625), the Natural Science Foundation of Fujian Province Grants (Project 2012J05154), and study abroad scholarships of Fujian Province.
Conflict of interest
The authors declare no financial or other conflicts of interest related to this study.
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