PMID- 26055049
OWN - NLM
STAT- MEDLINE
DCOM- 20161007
LR  - 20181113
IS  - 1573-6830 (Electronic)
IS  - 0272-4340 (Linking)
VI  - 36
IP  - 1
DP  - 2016 Jan
TI  - Abeta25-35 Suppresses Mitochondrial Biogenesis in Primary Hippocampal Neurons.
PG  - 83-91
LID - 10.1007/s10571-015-0222-6 [doi]
AB  - 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 (Abeta) 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-1alpha), the master regulator of mitochondrial biogenesis, is a target for SIRT1 
      deacetylase activity. In this study, we investigated the effects of Abeta25-35 on 
      mitochondrial biogenesis in cultured hippocampal neurons and the underlying 
      mechanisms. In primary hippocampal neurons, we found that 24-h incubation with 
      Abeta25-35 suppressed both phosphorylations of AMPK and SIRT1 expression and 
      increased PGC-1alpha acetylation expression. In addition, Abeta25-35 also resulted in a 
      decrease in mitochondrial DNA copy number, as well as decreases in the expression 
      of mitochondrial biogenesis factors (PGC-1alpha, NRF 1, NRF 2, and Tfam). Taken 
      together, these data show that Abeta25-35 suppresses mitochondrial biogenesis in 
      hippocampal neurons. Abeta25-35-induced impairment of mitochondrial biogenesis may 
      be associated with the inhibition of the AMPK-SIRT1-PGC-1alpha pathway.
FAU - Dong, Weiguo
AU  - Dong W
AD  - 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.
FAU - Wang, Feng
AU  - Wang F
AD  - Department of Integrated Traditional Chinese and Western Medicine, Fujian 
      University of Traditional Chinese Medicine, Fuzhou, 350122, Fujian, People's 
      Republic of China.
FAU - Guo, Wanqing
AU  - Guo W
AD  - The Third People's Hospital of Fujian Province, Fuzhou, 350122, Fujian, People's 
      Republic of China.
FAU - Zheng, Xuehua
AU  - Zheng X
AD  - Department of Integrated Traditional Chinese and Western Medicine, Fujian 
      University of Traditional Chinese Medicine, Fuzhou, 350122, Fujian, People's 
      Republic of China.
FAU - Chen, Yue
AU  - Chen Y
AD  - Department of Integrated Traditional Chinese and Western Medicine, Fujian 
      University of Traditional Chinese Medicine, Fuzhou, 350122, Fujian, People's 
      Republic of China.
FAU - Zhang, Wenguang
AU  - Zhang W
AD  - Department of Integrated Traditional Chinese and Western Medicine, Fujian 
      University of Traditional Chinese Medicine, Fuzhou, 350122, Fujian, People's 
      Republic of China.
FAU - Shi, Hong
AU  - Shi H
AD  - Department of Integrated Traditional Chinese and Western Medicine, Fujian 
      University of Traditional Chinese Medicine, Fuzhou, 350122, Fujian, People's 
      Republic of China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150609
PL  - United States
TA  - Cell Mol Neurobiol
JT  - Cellular and molecular neurobiology
JID - 8200709
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (DNA, Mitochondrial)
RN  - 0 (Peptide Fragments)
RN  - 0 (Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha)
RN  - 0 (Ppargc1a protein, rat)
RN  - 0 (RNA, Messenger)
RN  - 0 (Transcription Factors)
RN  - 0 (amyloid beta-protein (25-35))
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - EC 3.5.1.- (Sirtuin 1)
SB  - IM
MH  - AMP-Activated Protein Kinases/metabolism
MH  - Acetylation/drug effects
MH  - Amyloid beta-Peptides/*toxicity
MH  - Animals
MH  - Cell Death/drug effects
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - DNA, Mitochondrial/genetics
MH  - Down-Regulation/drug effects
MH  - Gene Dosage
MH  - Hippocampus/*cytology
MH  - Mitochondria/drug effects/*metabolism
MH  - Neurons/cytology/drug effects/*metabolism
MH  - *Organelle Biogenesis
MH  - Peptide Fragments/*toxicity
MH  - Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
MH  - Phosphorylation/drug effects
MH  - RNA, Messenger/genetics/metabolism
MH  - Rats, Sprague-Dawley
MH  - Sirtuin 1/metabolism
MH  - Transcription Factors/metabolism
OTO - NOTNLM
OT  - AMPK
OT  - Alzheimer's disease
OT  - Amyloid-beta
OT  - Mitochondrial biogenesis
OT  - PGC-1alpha
OT  - SIRT1
EDAT- 2015/06/10 06:00
MHDA- 2016/10/08 06:00
CRDT- 2015/06/10 06:00
PHST- 2015/03/15 00:00 [received]
PHST- 2015/06/02 00:00 [accepted]
PHST- 2015/06/10 06:00 [entrez]
PHST- 2015/06/10 06:00 [pubmed]
PHST- 2016/10/08 06:00 [medline]
AID - 10.1007/s10571-015-0222-6 [pii]
AID - 10.1007/s10571-015-0222-6 [doi]
PST - ppublish
SO  - Cell Mol Neurobiol. 2016 Jan;36(1):83-91. doi: 10.1007/s10571-015-0222-6. Epub 
      2015 Jun 9.