title: Geniposide regulates insulin-degrading enzyme expression to inhibit the cytotoxicity of Aβ₁₋₄₂ in cortical neurons.
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.
authors.affiliation: Research Centre of Medicinal Chemistry and Chemical Biology, Chongqing Technology and Business University, Chongqing 400067, PR China.
authors.forename: Fei
authors.initials: F
authors.lastname: Yin
authors.forename: Yonglan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Lixia
authors.initials: L
authors.lastname: Guo
authors.forename: Shuzhen
authors.initials: S
authors.lastname: Kong
authors.forename: Jianhui
authors.initials: J
authors.lastname: Liu
mesh_terms: D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000633:toxicity*; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D007339:Insulysin / Q000096:biosynthesis*; D039823:Iridoids / Q000494:pharmacology*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D016229:Amyloid beta-Peptides; D039823:Iridoids; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); C007835:geniposide; D007339:Insulysin