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CNS & Neurological Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5273
ISSN (Online): 1996-3181

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

Author(s): Fei Yin, Yonglan Zhang, Lixia Guo, Shuzhen Kong and Jianhui Liu

Volume 11, Issue 8, 2012

Page: [1045 - 1051] Pages: 7

DOI: 10.2174/1871527311211080015

Price: $65

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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.


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