title: Suppression of lipopolysaccharide-induced microglial activation by a benzothiazole derivative.
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.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul 138-736, Korea.
authors.forename: Eun-A
authors.initials: EA
authors.lastname: Kim
authors.forename: Hanwook
authors.initials: H
authors.lastname: Kim
authors.forename: Jee-Yin
authors.initials: JY
authors.lastname: Ahn
authors.forename: Hoh-Gyu
authors.initials: HG
authors.lastname: Hahn
authors.forename: Key-Sun
authors.initials: KS
authors.lastname: Kim
authors.forename: Tae Ue
authors.initials: TU
authors.lastname: Kim
authors.forename: Sung-Woo
authors.initials: SW
authors.lastname: Cho
mesh_terms: D000818:Animals; D052160:Benzothiazoles / Q000494:pharmacology*; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D008070:Lipopolysaccharides / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D051058:Oncogene Protein v-akt / Q000378:metabolism; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000378:metabolism
chemical_list: D052160:Benzothiazoles; D016207:Cytokines; C524157:KHG21834; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D052247:Nitric Oxide Synthase Type II; D051058:Oncogene Protein v-akt; D020928:Mitogen-Activated Protein Kinases