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08 December 2019 : Laboratory Research

Farnesoid X Receptor (FXR) Aggravates Amyloid-β-Triggered Apoptosis by Modulating the cAMP-Response Element-Binding Protein (CREB)/Brain-Derived Neurotrophic Factor (BDNF) Pathway In Vitro

Qingfa Chen1ABCDEG, Hongling Ma2BC, Xuewen Guo3BC, Jia Liu2BC, Ting Gui4BC, Zhibo Gai56ACDEF*

DOI: 10.12659/MSM.920065

Med Sci Monit 2019; 25:9335-9345

Abstract

BACKGROUND: Alzheimer’s disease (AD), which results in cognitive deficits, usually occurs in older people and is mainly caused by amyloid beta (Aβ) 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 Aβ. Co-immunoprecipitation was used to analyze the molecular partners involved in Aβ-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 Aβ-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 Aβ-triggered neuronal apoptosis effect and prevented the reduction in CREB and BDNF.

CONCLUSIONS: These data suggest that FXR regulates Aβ-induced neuronal apoptosis, which may be dependent on the CREB/BDNF signaling pathway in vitro.

Keywords: Alzheimer Disease, Brain-Derived Neurotrophic Factor, Cyclic AMP Response Element-Binding Protein, Farnesol

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750