Attenuation of beta-amyloid-induced neuroinflammation by KHG21834 in vivo.
Beta-Amyloid (ABeta)-induced neuroinflammation is one of the key events in the development of neurodegenerative disease. We previously reported that KHG21834, a benzothiazole derivative, attenuates ABeta-induced degeneration of cortical and mesencephalic neurons in vitro. In the present work, we show that KHG21834 reduces ABeta-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- 1Beta and tumor necrosis factor-alpha induced by ABeta 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 ABeta-mediated neuroinflammation.
Kim
Eun-A
EA
Department of Biochemistry, University of Ulsan College of Medicine, Seoul, Korea.
Hahn
Hoh-Gyu
HG
Kim
Tae Ue
TU
Choi
Soo Young
SY
Cho
Sung-Woo
SW
D016229:Amyloid beta-Peptides / Q000502:physiology*; D000818:Animals; D052160:Benzothiazoles / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007249:Inflammation / Q000209:etiology / Q000517:prevention & control*; D008636:Mesencephalon / Q000187:drug effects* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects / Q000473:pathology
D016229:Amyloid beta-Peptides; D052160:Benzothiazoles; C524157:KHG21834