PMID- 31812977
OWN - NLM
STAT- MEDLINE
DCOM- 20200521
LR  - 20200521
IS  - 1643-3750 (Electronic)
IS  - 1234-1010 (Print)
IS  - 1234-1010 (Linking)
VI  - 25
DP  - 2019 Dec 8
TI  - Farnesoid X Receptor (FXR) Aggravates Amyloid-beta-Triggered Apoptosis by Modulating 
      the cAMP-Response Element-Binding Protein (CREB)/Brain-Derived Neurotrophic 
      Factor (BDNF) Pathway In Vitro.
PG  - 9335-9345
LID - 10.12659/MSM.920065 [doi]
AB  - BACKGROUND Alzheimer's disease (AD), which results in cognitive deficits, usually 
      occurs in older people and is mainly caused by amyloid beta (Ass) deposits and 
      neurofibrillary tangles. The bile acid receptor, farnesoid X receptor (FXR), has 
      been extensively studied in cardiovascular diseases and digestive diseases. 
      However, the role of FXR in AD is not yet understood. The purpose of the present 
      study was to investigate the mechanism of FXR function in AD. MATERIAL AND 
      METHODS Lentivirus infection, flow cytometry, real-time PCR, and western blotting 
      were used to detect the gain or loss of FXR in cell apoptosis induced by Ass. 
      Co-immunoprecipitation was used to analyze the molecular partners involved in 
      Ass-induced apoptosis. RESULTS We found that the mRNA and protein expression of 
      FXR was enhanced in Ab-triggered neuronal apoptosis in differentiated SH-SY5Y 
      cells and in mouse hippocampal neurons. Overexpression of FXR aggravated 
      Ass-triggered neuronal apoptosis in differentiated SH-SY5Y cells, and this effect 
      was further increased by treatment with the FXR agonist 6ECDCA. Molecular 
      mechanism analysis by co-immunoprecipitation and immunoblotting revealed that FXR 
      interacted with the cAMP-response element-binding protein (CREB), leading to 
      decreased CREB and brain-derived neurotrophic factor (BDNF) protein levels. Low 
      expression of FXR mostly reversed the Ass-triggered neuronal apoptosis effect and 
      prevented the reduction in CREB and BDNF. CONCLUSIONS These data suggest that FXR 
      regulates Ass-induced neuronal apoptosis, which may be dependent on the CREB/BDNF 
      signaling pathway in vitro.
FAU - Chen, Qingfa
AU  - Chen Q
AD  - Institute for Tissue Engineering and Regenerative Medicine, Liaocheng 
      University/Liaocheng People's Hospital, Liaocheng, Shandong, China (mainland).
FAU - Ma, Hongling
AU  - Ma H
AD  - Department of Neurology, Liaocheng People's Hospital, Liaocheng, Shandong, China 
      (mainland).
FAU - Guo, Xuewen
AU  - Guo X
AD  - Department of Neurology, Dongchangfu People's Hospital/Second People's Hospital 
      of Liaocheng University, Liaocheng, Shandong, China (mainland).
FAU - Liu, Jia
AU  - Liu J
AD  - Department of Neurology, Liaocheng People's Hospital, Liaocheng, Shandong, China 
      (mainland).
FAU - Gui, Ting
AU  - Gui T
AD  - Key Laboratory of Traditional Chinese Medicine for Classical Theory, Ministry of 
      Education, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, 
      China (mainland).
FAU - Gai, Zhibo
AU  - Gai Z
AD  - Joint Pharmacology Center, Liaocheng People's Hospital, Liaocheng, Shandong, 
      China (mainland).
AD  - Department of Clinical Pharmacology and Toxicology, University Hospital Zurich, 
      University of Zurich, Zurich, Switzerland.
LA  - eng
PT  - Journal Article
DEP - 20191208
PL  - United States
TA  - Med Sci Monit
JT  - Medical science monitor : international medical journal of experimental and 
      clinical research
JID - 9609063
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (CREB1 protein, human)
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
RN  - 0 (Receptors, Cytoplasmic and Nuclear)
RN  - 0462Z4S4OZ (obeticholic acid)
RN  - 0C5V0MRU6P (farnesoid X-activated receptor)
RN  - 0GEI24LG0J (Chenodeoxycholic Acid)
RN  - 7171WSG8A2 (BDNF protein, human)
SB  - IM
MH  - Alzheimer Disease/*metabolism
MH  - Amyloid beta-Peptides/metabolism/physiology
MH  - Animals
MH  - Apoptosis/physiology
MH  - Brain/metabolism
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Cell Line
MH  - Chenodeoxycholic Acid/analogs & derivatives/pharmacology
MH  - Cyclic AMP Response Element-Binding Protein/metabolism
MH  - Disease Models, Animal
MH  - Hippocampus/metabolism
MH  - Humans
MH  - Mice
MH  - Neurons/metabolism
MH  - Receptors, Cytoplasmic and Nuclear/*metabolism/physiology
MH  - Signal Transduction/physiology
PMC - PMC6918812
COIS- Conflict of interest None.
EDAT- 2019/12/10 06:00
MHDA- 2020/05/22 06:00
PMCR- 2019/12/08
CRDT- 2019/12/09 06:00
PHST- 2019/12/09 06:00 [entrez]
PHST- 2019/12/10 06:00 [pubmed]
PHST- 2020/05/22 06:00 [medline]
PHST- 2019/12/08 00:00 [pmc-release]
AID - 920065 [pii]
AID - 10.12659/MSM.920065 [doi]
PST - epublish
SO  - Med Sci Monit. 2019 Dec 8;25:9335-9345. doi: 10.12659/MSM.920065.