Neuroprotective effects of N-adamantyl-4-methylthiazol-2-amine against amyloid beta-induced oxidative stress in mouse hippocampus

Abstract

We previously reported that N-adamantyl-4-methylthiazol-2-amine (KHG26693) suppresses amyloid beta (A beta)-induced neuronal oxidative damage in cortical neurons. Here we investigated the mechanism and antioxidative function of KHG26693 in the hippocampus of A beta-treated mice. KHG26693 significantly attenuated A beta-induced TNF-alpha and IL-1 beta enhancements. KHG26693 decreased A beta-mediated malondialdehyde formation, protein oxidation, and reactive oxygen species by decreasing the iNOS level. KHG26693 suppressed A beta-induced oxidative stress through a mechanism involving glutathione peroxidase, catalase, and GSH attenuation. A beta-induced MMP-2, cPLA2, and pcPLA2 expressions were almost completely attenuated by KHG26693 treatment, suggesting that A beta-induced oxidative stress reduction by KHG26693 is, at least partly, caused by the downregulation of MMP-2 and cPLA2 activation. Compared with A beta treatment, KHG26693 treatment upregulated Nrf2 and HO-1 expressions, suggesting that KHG26693 protects the brain from AP-induced oxidative damage, likely by maintaining redox balance through Nrf2/HO-1 pathway regulation. KHG26693 significantly attenuated A beta-induced oxidative stress in the hippocampus of A beta-treated mice. (C) 2016 Elsevier Inc. All rights reserved.