Suppression of lipopolysaccharide-induced microglial activation by a benzothiazole derivative

Molecules and Cells
Eun-A KimSung-Woo Cho

Abstract

We previously reported that KHG21834, a benzothiazole derivative, attenuates the beta-amyloid (Abeta)-induced degeneration of both cortical and mesencephalic neurons in vitro. Central nervous system inflammation mediated by activated microglia is a key event in the development of neurodegenerative disease. In this study, we show that KHG21834 suppresses inflammation-mediated cytokine upregulation. Specifically, KHG21834 induces significant reductions in the lipopolysaccharide-induced activation of microglia and production of proinflammatory mediators such as tumor necrosis factor-alpha, interlukin-1beta, nitric oxide, and inducible nitric oxide synthase. In addition, KHG21834 blocks the expression of mitogen-activated protein kinases, including ERK, p38 MAPK, JNK, and Akt. In vivo intracerebroventricular infusion of KHG21834 also leads to decreases the level of interleukin-1beta and tumor necrosis factor-alpha in brain. These results, in combination with our previous findings on Abeta-induced degeneration, support the potential therapeutic efficacy of KHG21834 for the treatment of neurodegenerative disorders via the targeting of key glial activation pathways.

References

Jan 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·E Puré, L Tardelli
Jan 2, 1991·Neuroscience Letters·J G Wood, P Zinsmeister
Dec 1, 1986·Journal of Pharmacological Methods·S E Laursen, J K Belknap
Jul 1, 1994·Journal of Neuropathology and Experimental Neurology·C S Raine
Apr 1, 1996·Current Opinion in Cell Biology·R Treisman
Mar 28, 1997·The Journal of Biological Chemistry·K ShirakabeE Nishida
May 15, 1998·Acta Paediatrica Japonica; Overseas Edition·L G Epstein
Apr 1, 1999·American Journal of Respiratory Cell and Molecular Biology·A B CarterG W Hunninghake
Apr 15, 1999·Annual Review of Neuroscience·F González-Scarano, G Baltuch
Jun 12, 1999·American Journal of Human Genetics·D Giulian
Mar 8, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·M Caivano, P Cohen
Aug 3, 2001·Nature Reviews. Neuroscience·D H SmallJ C Bornstein
Jan 30, 2002·Bioorganic & Medicinal Chemistry Letters·Chester A MathisWilliam E Klunk
Jul 20, 2002·Progress in Neurobiology·Chen Xu Wang, Ashfaq Shuaib
Aug 30, 2002·Proceedings of the National Academy of Sciences of the United States of America·Volker HeiserErich E Wanker
Oct 16, 2002·Glia·Milla Koistinaho, Jari Koistinaho
Nov 28, 2002·Advanced Drug Delivery Reviews·Amy H Moore, M K O'Banion
Dec 13, 2003·Biological Chemistry·Hartmut KleinertUlrich Förstermann
Mar 3, 2004·Journal of Neural Transmission·P Eikelenboom, W A van Gool
May 14, 2004·Neurochemical Research·Elena Ambrosini, Francesca Aloisi
Sep 24, 2004·The International Journal of Biochemistry & Cell Biology·Frederik Vilhardt
Oct 7, 2004·Neurobiology of Aging·Jeffrey M CraftLinda J Van Eldik
Jul 5, 2005·Neurobiology of Aging·Giovanna SebastianiPatrick Tremblay
Jul 22, 2005·Nature Reviews. Immunology·Stuart M AllanNancy J Rothwell

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Citations

May 28, 2011·Cellular and Molecular Neurobiology·Hanwook KimSung-Woo Cho

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