Kim, Hyeon Jeong Jang, Bo Ko Park, Jong-Hyun Choi, Ji Won Park, Sun Jun Byeon, Seong Rim Pae, Ae Nim Lee, Yang Sup Cheong, Eunji Park, Ki Duk 2024-01-19T18:30:53Z 2024-01-19T18:30:53Z 2021-09-05 2020-01-01 0223-5234 https://pubs.kist.re.kr/handle/201004/119105 Alzheimer's disease is a common neurodegenerative disease characterized by progressive degeneration and neuronal cell death, resulting in neural network dysfunction. As the underlying mechanisms, oxidative damage and neuroinflammation have been reported to contribute to the onset and deterioration of Alzheimer's disease. The nuclear factor E2-related factor 2-antioxidant responsive element signaling pathway is a pivotal cellular defense mechanism against oxidative stress. Nrf2, a transcription factor, regulates the cellular redox balance and is primarily involved in anti-inflammatory responses. In this study, we synthesized novel chalcone derivatives and found a highly potent Nrt2 activator, compound 20a. Compound 20a confirmed to activate Nrf2 and induce expression of the Nrf2-dependent enzymes HO-1 and GCLC at both mRNA and protein levels. It also suppressed the production of nitric oxide and downregulated inflammatory mediators in BV-2 microglial cells. We found that compound 20a effectively increased the expression level and the activity of superoxide dismutase in both BV-2 microglial cells and brain hippocampus region of the scopolamine-induced mouse model. In addition, compound 20a effectively recovered the learning and memory impairment in a scopolamine-induced mouse model. (C) 2019 Elsevier Masson SAS. All rights reserved. English ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER NF-KAPPA-B OXIDATIVE STRESS ALZHEIMERS-DISEASE SIGNALING PATHWAY INDUCED AMNESIA EXPRESSION INFLAMMATION ACID ANTIOXIDANT INHIBITION A novel chalcone derivative as Nrf2 activator attenuates learning and memory impairment in a scopolamine-induced mouse model Article 10.1016/j.ejmech.2019.111777 1 EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, v.185 EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 185 scie scopus 000503099900019 2-s2.0-85073827651 Chemistry, Medicinal Pharmacology & Pharmacy Article NF-KAPPA-B OXIDATIVE STRESS ALZHEIMERS-DISEASE SIGNALING PATHWAY INDUCED AMNESIA EXPRESSION INFLAMMATION ACID ANTIOXIDANT INHIBITION Alzheimer&apos s disease Nuclear factor erythroid 2-related factor 2 Chalcone Oxidative stress Superoxide dismutase