Antioxidative effects of ethyl 2-(3-(benzo[d]thiazol-2-yl)ureido)acetate against amyloid beta-induced oxidative cell death via NF-kappa B, GSK-3 beta and beta-catenin signaling pathways in cultured cortical neurons

摘要

We have previously shown that 2-(3-(benzo[d]thiazol-2-yl)ureido) acetate (KHG21834) attenuates amyloid beta(A beta)(25-35)-induced apoptotic death and shows anti-inflammatory activity against A beta(25-35)-induced microglial activation. However, antioxidative effects of KHG21834 against A beta-induced oxidative stress have not yet been reported. In the present study, we investigated the antioxidative function of KHG21834 in primary cultured cortical neurons, to expand the potential therapeutic efficacy of KHG21834. Pretreatment with KHG21834 protected against A beta-induced neuronal cell death and mitochondrial damage, and significantly restored GSH levels and the activities of catalase, superoxide dismutase, and glutathione peroxidase, and also suppressed the production of reactive oxygen species and protein oxidation. These results imply that KHG21834 may play a role in cellular defense mechanisms against A beta-induced oxidative stress in cultured cortical neurons. Furthermore, KHG21834 significantly attenuated the effects of A beta treatment on levels of NF-kappa B, beta-catenin, and GSK-3 beta proteins in cortical neurons. Taken together, our results suggest that the antioxidant effects of KHG21834 may result at least in part from its ability to regulate the NF-kappa B, beta-catenin, and GSK-3 beta signaling pathways. To our knowledge, this is the first report showing that KHG21834 significantly attenuates A beta(25-35)-induced oxidative stress in primary cortical neurons, and provides novel insights into KHG21834 as a possible therapeutic agent for the treatment of A beta-mediated neurotoxicity involving oxidative stress.