N-Adamantyl-4-methylthiazol-2-amine suppresses amyloid β-induced neuronal oxidative damage in cortical neurons

Abstract

Recently, we have reported that N-adamantyl-4-methylthiazol-2-amine (KHG26693) successfully reduced the production of oxidative stress in streptozotocin-induced diabetic rats and lipopolysaccharide-induced BV-2 microglial cells by increasing their antioxidant capacity. However, antioxidative effects of KHG26693 against Aβ (Aβ)-induced oxidative stress have not yet been reported. In the present study, we further investigated the antioxidative function of KHG26693 in Aβ-mediated primary cultured cortical neurons. We showed here that KHG26693 attenuated Aβ-induced cytotoxicity, increase of Bax/Bcl-2 ratio, elevation of caspase-3 expression, and impairment of mitochondrial membrane potential in cultured primary cortical neurons. KHG26693 also decreases the Aβ-mediated formation of malondialdehyde, reactive oxygen species, and NO production by decreasing nitric oxide synthase (iNOS) and NADPH oxidase level. Moreover, KHG26693 suppress the Aβ-induced oxidative stress through a possible mechanism involving attenuation of GSH and antioxidant enzyme activities such as glutathione reductase and glutathione peroxidase (GPx). Finally, pretreatment of cortical neurons with KHG26693 significantly reduced the Aβ-induced protein oxidation and nitration. To our knowledge, this is the first report, showing that KHG26693 significantly attenuates Aβ-induced oxidative stress in primary cortical neurons, and may prove attractive strategies to reduce Aβ-induced neural cell death.

Keywords:

• Alzheimer’s disease
• beta-amyloid
• N-adamantyl-4-methylthiazol-2-amine
• oxidative stress

Disclosure statement

The authors declare no conflicts of interest.

Funding information

This work was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2015R1D1A1A09056947 and 2015R1D1A3A01015793) and by Student Research Grants from the University of Ulsan College of Medicine, Seoul, Korea.