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

Abstract

We have previously shown that 2-(3-(benzo[d]thiazol-2-yl)ureido)acetate (KHG21834) attenuates amyloid beta(Aβ)_25–35-induced apoptotic death and shows anti-inflammatory activity against Aβ_25–35-induced microglial activation. However, antioxidative effects of KHG21834 against Aβ-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 Aβ-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 Aβ-induced oxidative stress in cultured cortical neurons. Furthermore, KHG21834 significantly attenuated the effects of Aβ treatment on levels of NF-κB, β-catenin, and GSK-3β 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-κB, β-catenin, and GSK-3β signaling pathways. To our knowledge, this is the first report showing that KHG21834 significantly attenuates Aβ_25–35-induced oxidative stress in primary cortical neurons, and provides novel insights into KHG21834 as a possible therapeutic agent for the treatment of Aβ-mediated neurotoxicity involving oxidative stress.

Keywords::

• beta-amyloid
• Alzheimer's disease
• oxidative stress
• KHG21834
• NF-κB
• GSK-3β

Acknowledgements

This work was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Education (2012R1A1A2041484) and by a Student Research Grant from the University Of Ulsan College Of Medicine, Seoul, Korea.

Declaration of interest

The authors declare no conflicts of interest.