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Abstract Title:

Panaxadiol inhibits synaptic dysfunction in Alzheimer's disease and targets the Fyn protein in APP/PS1 mice and APP-SH-SY5Y cells.

Abstract Source:

Life Sci. 2019 Mar 15 ;221:35-46. Epub 2019 Feb 5. PMID: 30735733

Abstract Author(s):

Xicai Liang, Yingjia Yao, Ying Lin, Liang Kong, Honghe Xiao, Yue Shi, Jingxian Yang

Article Affiliation:

Xicai Liang

Abstract:

AIM: Alzheimer's disease (AD), a neurodegenerative disease, is characterized by memory loss and synaptic damage. Up to now, there are limited drugs to cure or delay the state of this illness. Recently, the Fyn tyrosine kinase is implicated in AD pathology triggered by synaptic damage. Thus, Fyn inhibition may prevent or delay the AD progression. Therefore, in this paper, we investigated whether Panaxadiol could decrease synaptic damage in AD and the underlying mechanism.

MAIN METHODS: The ability of learning and memory of mice has detected by Morris Water Maze. The pathological changes detected by H&E staining and Nissl staining. The percentage of cell apoptosis and the calcium concentration were detected by Flow Cytometry in vitro. The amount of synaptic protein and related proteins in the Fyn/GluN2B/CaMKIIα signaling pathway were detected by Western Blot.

KEY FINDINGS: In the present article, Panaxadiol could significantly improve the ability of learning and memory of mice and reduce its synaptic dysfunction. Panaxadiol could down-regulate GluN2B's phosphorylation level by inhibition Fyn kinase activity, Subsequently, decrease Ca-mediated synaptic damage, reducing LDH leakage, inhibiting apoptosis in AD, resulting in facilitating the cells survival. For the underlying molecular mechanism, we used PP2 to block the Fyn/GluN2B/CaMKIIα signaling pathway. The results from WB showed that the expression of related proteins in the Fyn signaling pathway decreased with PP2 treated.

SIGNIFICANCE: Our results indicate that Panaxadiol could decrease synaptic damage, which will cause AD via inhibition of the Fyn/GluN2B/CaMKIIα signaling pathway. Thus, the Panaxadiol is a best promising candidate to test as a potential therapy for AD.

Study Type : Animal Study

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