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Current Alzheimer Research
ISSN (Print): 1567-2050
ISSN (Online): 1875-5828
VOLUME: 11
ISSUE: 5
DOI: 10.2174/1567205011666140514111204      Price:  $58









Geniposide Attenuates Oligomeric Aβ1-42-Induced Inflammatory Response by Targeting RAGE-Dependent Signaling in BV2 Cells

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Author(s): Cui Lv, Lei Wang, Xiaoli Liu, Xiao Cong, Shirley ShiDu Yan, Yongyan Wang and Wensheng Zhang
Pages 430-440 (11)
Abstract:
The neuroinflammation induced by amyloid-β (Aβ) is one of the key events in Alzheimer’s disease (AD) progress in which microglia are the main cells involved. Receptor for advanced glycation end products (RAGE) mediates and enhances Aβ-induced microglial activation and leads to induction of proinflammatory mediators, such as tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). Geniposide, a pharmacologically active component purified from gardenia fruit, exhibits a broad spectrum anti-inflammatory effect as well as neurotrophic and neuroprotective properties. However, the effects of geniposide on Aβ-mediated microglial pathways have not been fully discovered. Here, we demonstrate that geniposide treatment significantly blocks Aβ-induced RAGE-dependent signaling (activation of ERK and NF-κB) along with the production of TNF-α and IL-1β in cultured BV2 microglia cells. Notably, based on the data from coimmunoprecipitation assay, we infer that geniposide exerts protective effects on Aβ-induced inflammatroy response through blocking Aβ binding to RAGE and suppressing the RAGE-mediated signaling pathway. Taken together, these findings indicate that geniposide is a potent suppressor of neuroflammation through inhibiting RAGE-dependent signaling pathway. Thus, geniposide may be a potential therapeutic agent for the treatment of neuroinflammation that is involved in neurological diseases such as AD.
Keywords:
Alzheimer’s disease, geniposide, inflammatory responses, oligomeric Aβ1-42, RAGE, RAGE-dependent signaling pathway.
Affiliation:
C Building, Beijing Normal University Science Park, No. 12, Xueyuan Southern Street, Haidian District, Beijing, P.R.China, 100088.