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Geniposide Regulates Insulin-Degrading Enzyme Expression to Inhibit the Cytotoxicity of Aβ1-42 in Cortical Neurons

[ Vol. 11 , Issue. 8 ]

Author(s):

Fei Yin, Yonglan Zhang, Lixia Guo, Shuzhen Kong and Jianhui Liu   Pages 1045 - 1051 ( 7 )

Abstract:


We reported previously that geniposide showed neurotrophic and neuroprotective activities with the activation of glucagons-like peptide 1 receptor (GLP-1R) in neurons. The current study was designed to further investigate the protective effect of geniposide on β-amyloid (Aβ)-induced cytotoxicity. Our results showed that pre-incubation with geniposide prevented Aβ1-42-induced cell injury in primary cultured cortical neurons. Geniposide also induced the expression of insulin-degrading enzyme (IDE), a major degrading protease of Aβ, in a dose-dependent manner. Moreover, bacitracin, an inhibitor of IDE, and RNAi on Glp-1r gene decreased the neuroprotection of geniposide in Aβ1-42-treated cortical neurons. Our findings indicated that geniposide activating GLP-1R to against Aβ-induced neurotoxicity involved in its regulation on the expression of IDE in cortical neurons, which provided an additional mechanistic insight into the role of GLP-1R in neuroprotection.

Keywords:

Alzheimer’s disease (AD), β-amyloid (Aβ), glucagon-like peptide 1 receptor (GLP-1R), insulin-degrading enzyme (IDE), neuroprotection, neurotoxicity, cortical neurons, protease, endogenous, horseradish peroxidase.

Affiliation:

Research Centre of Medicinal Chemistry and Chemical Biology, Chongqing Technology and Business University, Chongqing 400067, P.R. China.



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