Tripchlorolide protects neuronal cells from microglia-mediated β-amyloid neurotoxicity through inhibiting NF-κB and JNK signaling

Authors

  • Xiao-Dong Pan,

    1. Department of Neurology, Union Hospital of Fujian Medical University, Fuzhou, Fujian, People's Republic of China
    2. Fujian Institute of Geriatrics, Fuzhou, Fujian, People's Republic of China
    3. Centre of Neurobiology of Fujian Medical University, Fuzhou, Fujian, People's Republic of China
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  • Xiao-Chun Chen,

    Corresponding author
    1. Department of Neurology, Union Hospital of Fujian Medical University, Fuzhou, Fujian, People's Republic of China
    2. Fujian Institute of Geriatrics, Fuzhou, Fujian, People's Republic of China
    3. Centre of Neurobiology of Fujian Medical University, Fuzhou, Fujian, People's Republic of China
    • Department of Neurology, Union Hospital of Fujian Medical University, 29 Xinquan Road, Fuzhou, Fujian 350001, People's Republic of China
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  • Yuan-Gui Zhu,

    1. Fujian Institute of Geriatrics, Fuzhou, Fujian, People's Republic of China
    2. Centre of Neurobiology of Fujian Medical University, Fuzhou, Fujian, People's Republic of China
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  • Li-Min Chen,

    1. Fujian Institute of Geriatrics, Fuzhou, Fujian, People's Republic of China
    2. Centre of Neurobiology of Fujian Medical University, Fuzhou, Fujian, People's Republic of China
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  • Jing Zhang,

    1. Fujian Institute of Geriatrics, Fuzhou, Fujian, People's Republic of China
    2. Centre of Neurobiology of Fujian Medical University, Fuzhou, Fujian, People's Republic of China
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  • Tian-Wen Huang,

    1. Department of Neurology, Union Hospital of Fujian Medical University, Fuzhou, Fujian, People's Republic of China
    2. Fujian Institute of Geriatrics, Fuzhou, Fujian, People's Republic of China
    3. Centre of Neurobiology of Fujian Medical University, Fuzhou, Fujian, People's Republic of China
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  • Qin-Yong Ye,

    1. Department of Neurology, Union Hospital of Fujian Medical University, Fuzhou, Fujian, People's Republic of China
    2. Centre of Neurobiology of Fujian Medical University, Fuzhou, Fujian, People's Republic of China
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  • Hua-Pin Huang

    1. Department of Neurology, Union Hospital of Fujian Medical University, Fuzhou, Fujian, People's Republic of China
    2. Centre of Neurobiology of Fujian Medical University, Fuzhou, Fujian, People's Republic of China
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Abstract

Recent research has focused on soluble oligomeric assemblies of β-amyloid peptides (Aβ) as the proximate cause of neuroinflammation, synaptic loss, and the eventual dementia associated with Alzheimer's disease (AD). In this study, tripchlorolide (T4), an extract of Tripterygium wilfordii Hook. F (TWHF), was studied as a novel agent to suppress neuroinflammatory process in microglial cells and to protect neuronal cells against microglia-mediated oligomeric Aβ toxicity. T4 significantly attenuated oligomeric Aβ(1-42)-induced release of inflammatory productions such as tumor necrosis factor-α, interleukin-1β, nitric oxide (NO), and prostaglandin E2. It also downregulated the protein levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in microglial cells. Further molecular mechanism study demonstrated that T4 inhibited the nuclear translocation of nuclear factor-κB (NF-κB) without affecting I-κBα phosphorylation. It repressed Aβ-induced JNK phosphorylation but not ERK or p38 MAPK. The inhibition of NF-κB and JNK by T4 is correlated with the suppression of inflammatory mediators in Aβ-stimulated microglial cells. These results suggest that T4 protects neuronal cells by blocking inflammatory responses of microglial cells to oligomeric Aβ(1-42) and that T4 acts on the signaling of NF-κB and JNK, which are involved in the modulation of inflammatory response. Therefore, T4 may be an effective agent in modulating neuroinflammatory process in AD. © 2009 Wiley-Liss, Inc.

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