{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T00:15:46Z","timestamp":1776644146893,"version":"3.51.2"},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2024,9,11]],"date-time":"2024-09-11T00:00:00Z","timestamp":1726012800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Takeda Foundation, the Naito Foundation, and the Spanish Ministry of Economy and Competitiveness","award":["PID2022\u2013141786OB-I00"],"award-info":[{"award-number":["PID2022\u2013141786OB-I00"]}]},{"name":"Basis for Supporting Innovative Drug Discovery and Life Science Research (BINDS) from the AMED","award":["JP23ama121038"],"award-info":[{"award-number":["JP23ama121038"]}]},{"name":"Grants-in-Aid for JSPS","award":["19H05649 and 23\u00a0K10820"],"award-info":[{"award-number":["19H05649 and 23\u00a0K10820"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,11,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Alzheimer\u2019s disease (AD) is the most common aetiology of dementia. The transcription factor NF-E2-related factor 2 (NRF2) induces the expression of genes encoding phase II detoxification and antioxidant genes. NRF2 is regulated by Kelch-like ECH-associated protein 1 (KEAP1), and the KEAP1-NRF2 system is the key regulatory system involved in cytoprotection. To examine whether pharmacological induction of NRF2 expression alleviates AD phenotypes in vivo, we employed two AD mouse models, i.e. App \u00a0NL-G-F\/NL-G-F (AppNLGF) and APPV717I::TAUP301L (APP\/TAU) mice. As the synthetic oleanane triterpenoid 1-[2-cyano-3,12-dioxooleana-1,9(11-dien-28-oyl)] (CDDO)-4(\u2212pyridin-2-yl)-imidazole (CDDO-2P-Im) exhibits strong NRF2-inducing activity, we treated AD model mice with CDDO-2P-Im. We found that A\u03b242 levels were markedly greater in the brains of AppNLGF mice than in those of APP\/TAU mice. CDDO-2P-Im treatment significantly decreased A\u03b242 levels, but not A\u03b240 levels, in APP\/TAU mice. Consequently, CDDO-2P-Im also decreased the ratio of A\u03b242\/A\u03b240, a vital marker of amyloid plaque formation. LC\u2013MS\/MS analyses revealed that CDDO-2P-Im was delivered to the brains of the APP\/TAU mice. CDDO-2P-Im induced the expression of detoxification and antioxidant gene targets of NRF2 and elevated reduced glutathione (GSH) levels in the mouse brain. These results support the notion that CDDO-2P-Im ameliorates AD-related pathologic changes.<\/jats:p>","DOI":"10.1093\/jb\/mvae060","type":"journal-article","created":{"date-parts":[[2024,9,11]],"date-time":"2024-09-11T22:33:08Z","timestamp":1726093988000},"page":"405-414","source":"Crossref","is-referenced-by-count":6,"title":["The NRF2 inducer CDDO-2P-Im provokes a reduction in amyloid \u03b2 levels in Alzheimer\u2019s disease model mice"],"prefix":"10.1093","volume":"176","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9224-0161","authenticated-orcid":false,"given":"Akira","family":"Uruno","sequence":"first","affiliation":[{"name":"Tohoku University Department of Integrative Genomics, Tohoku Medical Megabank Organization, , 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8573,","place":["Japan"]},{"name":"Tohoku University Department of Biochemistry and Molecular Biology, Tohoku Medical Megabank Organization, , 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8573,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shiori","family":"Kadoguchi-Igarashi","sequence":"additional","affiliation":[{"name":"Tohoku University Department of Biochemistry and Molecular Biology, Tohoku Medical Megabank Organization, , 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8573,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ritsumi","family":"Saito","sequence":"additional","affiliation":[{"name":"Tohoku University Department of Integrative Genomics, Tohoku Medical Megabank Organization, , 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8573,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shohei","family":"Koiso","sequence":"additional","affiliation":[{"name":"Tohoku University Department of Biochemistry and Molecular Biology, Tohoku Medical Megabank Organization, , 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8573,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daisuke","family":"Saigusa","sequence":"additional","affiliation":[{"name":"Tohoku University Department of Integrative Genomics, Tohoku Medical Megabank Organization, , 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8573,","place":["Japan"]},{"name":"Teikyo University Department of Pharma-Sciences, , 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ching-Tung","family":"Chu","sequence":"additional","affiliation":[{"name":"Tohoku University Department of Biochemistry and Molecular Biology, Tohoku Medical Megabank Organization, , 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8573,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takafumi","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Tohoku University Department of Integrative Genomics, Tohoku Medical Megabank Organization, , 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8573,","place":["Japan"]},{"name":"Tohoku University Department of Biochemistry and Molecular Biology, Tohoku Medical Megabank Organization, , 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8573,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9659-9251","authenticated-orcid":false,"given":"Takashi","family":"Saito","sequence":"additional","affiliation":[{"name":"Nagoya City University Department of Neurocognitive Science, Institute of Brain Science, , 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takaomi C","family":"Saido","sequence":"additional","affiliation":[{"name":"RIKEN Brain Science Institute Laboratory for Proteolytic Neuroscience, , 2-1 Hirosawa, Wako 351-0198,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio","family":"Cuadrado","sequence":"additional","affiliation":[{"name":"Autonomous University of Madrid, Instituto de Investigaci\u00f3n Sanitaria La Paz (IdiPaz), Centro de Investigaci\u00f3n Biom\u00e9dica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), ISCIII Department of Biochemistry, Faculty of Medicine, , Duperier, 4, Madrid 28049,","place":["Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masayuki","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Tohoku University Department of Integrative Genomics, Tohoku Medical Megabank Organization, , 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8573,","place":["Japan"]},{"name":"Tohoku University Department of Biochemistry and Molecular Biology, Tohoku Medical Megabank Organization, , 2-1 Seiryo-machi, Aoba-ku, Sendai 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