A beta 25-35 Suppresses Mitochondrial Biogenesis in Primary Hippocampal Neurons

作者：Dong, Weiguo^*; Wang, Feng; Guo, Wanqing; Zheng, Xuehua; Chen, Yue; Zhang, Wenguang; Shi, Hong

来源：Cellular and Molecular Neurobiology, 2016, 36(1): 83-91.

DOI：10.1007/s10571-015-0222-6

• Alzheimer's disease
• Mitochondrial biogenesis
• Amyloid-beta
• AMPK
• SIRT1
• PGC-1 alpha

Mitochondrial biogenesis is involved in the regulation of mitochondrial content, morphology, and function. Impaired mitochondrial biogenesis has been observed in Alzheimer's disease. Amyloid-beta (A beta) 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-gamma coactivator 1-alpha (PGC-1 alpha), the master regulator of mitochondrial biogenesis, is a target for SIRT1 deacetylase activity. In this study, we investigated the effects of A beta 25-35 on mitochondrial biogenesis in cultured hippocampal neurons and the underlying mechanisms. In primary hippocampal neurons, we found that 24-h incubation with A beta 25-35 suppressed both phosphorylations of AMPK and SIRT1 expression and increased PGC-1 alpha acetylation expression. In addition, A beta 25-35 also resulted in a decrease in mitochondrial DNA copy number, as well as decreases in the expression of mitochondrial biogenesis factors (PGC-1 alpha, NRF 1, NRF 2, and Tfam). Taken together, these data show that A beta 25-35 suppresses mitochondrial biogenesis in hippocampal neurons. A beta 25-35-induced impairment of mitochondrial biogenesis may be associated with the inhibition of the AMPK-SIRT1-PGC-1 alpha pathway.

• 出版日期2016-1
• 单位福建中医药大学