title: 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.
authors.affiliation: a Department of Biochemistry and Molecular Biology , University of Ulsan College of Medicine , Seoul , Republic of Korea ;
authors.forename: Chang Hun
authors.initials: CH
authors.lastname: Cho
authors.affiliation: b Department of Biomedical Laboratory Science , Konyang University , Daejeon , Republic of Korea ;
authors.forename: Eun-A
authors.initials: EA
authors.lastname: Kim
authors.affiliation: a Department of Biochemistry and Molecular Biology , University of Ulsan College of Medicine , Seoul , Republic of Korea ;
authors.forename: Jiae
authors.initials: J
authors.lastname: Kim
authors.affiliation: c Department of Biomedical Science and Research Institute for Bioscience and Biotechnology , Hallym University , Chunchon , Republic of Korea.
authors.forename: Soo Young
authors.initials: SY
authors.lastname: Choi
authors.affiliation: b Department of Biomedical Laboratory Science , Konyang University , Daejeon , Republic of Korea ;
authors.forename: Seung-Ju
authors.initials: SJ
authors.lastname: Yang
authors.affiliation: a Department of Biochemistry and Molecular Biology , University of Ulsan College of Medicine , Seoul , Republic of Korea ;
authors.forename: Sung-Woo
authors.initials: SW
authors.lastname: Cho
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives* / Q000378:metabolism; D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D009474:Neurons / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D013844:Thiazoles / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; C000594799:N-adamantyl-4-methylthiazol-2-amine; D013844:Thiazoles; D000218:Adamantane
keywords: Alzheimer’s disease; N-adamantyl-4-methylthiazol-2-amine; beta-amyloid; oxidative stress