Neuroprotective effects of N-adamantyl-4-methylthiazol-2-amine against amyloid β-induced oxidative stress in mouse hippocampus.
We previously reported that N-adamantyl-4-methylthiazol-2-amine (KHG26693) suppresses amyloid beta (Aβ)-induced neuronal oxidative damage in cortical neurons. Here we investigated the mechanism and antioxidative function of KHG26693 in the hippocampus of Aβ-treated mice. KHG26693 significantly attenuated Aβ-induced TNF-α and IL-1β enhancements. KHG26693 decreased Aβ-mediated malondialdehyde formation, protein oxidation, and reactive oxygen species by decreasing the iNOS level. KHG26693 suppressed Aβ-induced oxidative stress through a mechanism involving glutathione peroxidase, catalase, and GSH attenuation. Aβ-induced MMP-2, cPLA2, and pcPLA2 expressions were almost completely attenuated by KHG26693 treatment, suggesting that Aβ-induced oxidative stress reduction by KHG26693 is, at least partly, caused by the downregulation of MMP-2 and cPLA2 activation. Compared with Aβ treatment, KHG26693 treatment upregulated Nrf2 and HO-1 expressions, suggesting that KHG26693 protects the brain from Aβ-induced oxidative damage, likely by maintaining redox balance through Nrf2/HO-1 pathway regulation. KHG26693 significantly attenuated Aβ-induced oxidative stress in the hippocampus of Aβ-treated mice.
Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul, 05505, Republic of Korea.
Jiae
J
Kim
Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul, 05505, Republic of Korea.
Chang Hun
CH
Cho
Chemical Kinomics Research Center, Korea Institute of Science and Technology, Seoul, 02456, Republic of Korea.
Hoh-Gyu
HG
Hahn
Department of Biomedical Science and Research Institute for Bioscience and Biotechnology, Hallym University, Chunchon, 24252, Republic of Korea.
Soo-Young
SY
Choi
Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul, 05505, Republic of Korea. Electronic address: swcho@amc.seoul.kr.
Sung-Woo
SW
Cho
D000218:Adamantane / Q000031:analogs & derivatives* / Q000494:pharmacology; D016229:Amyloid beta-Peptides / Q000633:toxicity; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D002374:Catalase / Q000378:metabolism; D005260:Female; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D054513:Group IV Phospholipases A2 / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D008810:Mice, Inbred C57BL; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D010446:Peptide Fragments / Q000633:toxicity; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D013844:Thiazoles / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016229:Amyloid beta-Peptides; D000893:Anti-Inflammatory Agents; D000975:Antioxidants; C587672:IL1B protein, mouse; D053583:Interleukin-1beta; D008565:Membrane Proteins; C000594799:N-adamantyl-4-methylthiazol-2-amine; D051267:NF-E2-Related Factor 2; D018696:Neuroprotective Agents; C495636:Nfe2l2 protein, mouse; D010446:Peptide Fragments; D017382:Reactive Oxygen Species; D013844:Thiazoles; D014409:Tumor Necrosis Factor-alpha; C074636:amyloid beta-protein (25-35); D002374:Catalase; D005979:Glutathione Peroxidase; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse; D013482:Superoxide Dismutase; D054513:Group IV Phospholipases A2; D020778:Matrix Metalloproteinase 2; C522362:Mmp2 protein, mouse; D005978:Glutathione; D000218:Adamantane
Alzheimer’s disease; Amyloid β; N-Adamantyl-4-methylthiazol-2-amine; Oxidative stress