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Attenuation of β-amyloid-induced neuroinflammation by KHG21834 in vivo

  • Kim, Eun-A (Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine) ;
  • Hahn, Hoh-Gyu (Life Sciences, Korea Institute of Science and Technology) ;
  • Kim, Tae-Ue (Biomedical Laboratory Science, Yonsei University) ;
  • Choi, Soo-Young (Biomedical Sciences and Research Institute for Bioscience and Biotechnology, Hallym University) ;
  • Cho, Sung-Woo (Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine)
  • Received : 2010.03.30
  • Accepted : 2010.04.08
  • Published : 2010.06.30

Abstract

Beta-Amyloid ($A{\beta}$)-induced neuroinflammation is one of the key events in the development of neurodegenerative disease. We previously reported that KHG21834, a benzothiazole derivative, attenuates $A{\beta}$-induced degeneration of cortical and mesencephalic neurons in vitro. In the present work, we show that KHG21834 reduces $A{\beta}$-mediated neuroinflammation in brain. In vivo intracerebroventricular infusion of KHG21834 leads to decreases in the numbers of activated astrocytes and microglia and level of proinflammatory cytokines such as interleukin-$1{\beta}$ and tumor necrosis factor-$\alpha$ induced by $A{\beta}$ in the hippocampus. This suppression of neuroinflammation is associated with decreased neuron loss, restoration of synaptic dysfunction biomarkers in the hippocampus to control level, and diminished amyloid deposition. These results may suggest the potential therapeutic efficacy of KHG21834 for the treatment of $A{\beta}$-mediated neuroinflammation.

Keywords

References

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