title: Aβ25-35 Suppresses Mitochondrial Biogenesis in Primary Hippocampal Neurons.
abstract: 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.
authors.affiliation: Department of Integrated Traditional Chinese and Western Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, Fujian, People's Republic of China. fjdwg601@163.com.
authors.forename: Weiguo
authors.initials: W
authors.lastname: Dong
authors.affiliation: Department of Integrated Traditional Chinese and Western Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, Fujian, People's Republic of China.
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.affiliation: The Third People's Hospital of Fujian Province, Fuzhou, 350122, Fujian, People's Republic of China.
authors.forename: Wanqing
authors.initials: W
authors.lastname: Guo
authors.affiliation: Department of Integrated Traditional Chinese and Western Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, Fujian, People's Republic of China.
authors.forename: Xuehua
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Department of Integrated Traditional Chinese and Western Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, Fujian, People's Republic of China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Integrated Traditional Chinese and Western Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, Fujian, People's Republic of China.
authors.forename: Wenguang
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Integrated Traditional Chinese and Western Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, Fujian, People's Republic of China.
authors.forename: Hong
authors.initials: H
authors.lastname: Shi
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000107:Acetylation / Q000187:drug effects; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004272:DNA, Mitochondrial / Q000235:genetics; D015536:Down-Regulation / Q000187:drug effects; D018628:Gene Dosage; D006624:Hippocampus / Q000166:cytology*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D001678:Organelle Biogenesis; D010446:Peptide Fragments / Q000633:toxicity*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D056564:Sirtuin 1 / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D004272:DNA, Mitochondrial; D010446:Peptide Fragments; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D012333:RNA, Messenger; D014157:Transcription Factors; C074636:amyloid beta-protein (25-35); D055372:AMP-Activated Protein Kinases; D056564:Sirtuin 1
keywords: AMPK; Alzheimer’s disease; Amyloid-β; Mitochondrial biogenesis; PGC-1α; SIRT1