{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:48:02Z","timestamp":1787028482701,"version":"build-2736575974"},"reference-count":56,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2022,9,13]],"date-time":"2022-09-13T00:00:00Z","timestamp":1663027200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"Korean government (MSIT)","doi-asserted-by":"publisher","award":["2020M3A9E4104384"],"award-info":[{"award-number":["2020M3A9E4104384"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) is a form of dementia associated with abnormal glucose metabolism resulting from amyloid-beta (A\u03b2) plaques and intracellular neurofibrillary tau protein tangles. In a previous study, we confirmed that carboxy-dehydroevodiamine\u2219HCl (cx-DHED), a derivative of DHED, was effective at improving cognitive impairment and reducing phosphorylated tau levels and synaptic loss in an AD mouse model. However, the specific mechanism of action of cx-DHED is unclear. In this study, we investigated how the cx-DHED attenuates AD pathologies in the 5xFAD mouse model, focusing particularly on abnormal glucose metabolism. We analyzed behavioral changes and AD pathologies in mice after intraperitoneal injection of cx-DHED for 2 months. As expected, cx-DHED reversed memory impairment and reduced A\u03b2 plaques and astrocyte overexpression in the brains of 5xFAD mice. Interestingly, cx-DHED reversed the abnormal expression of glucose transporters in the brains of 5xFAD mice. In addition, otherwise low O-GlcNac levels increased, and the overactivity of phosphorylated GSK-3\u03b2 decreased in the brains of cx-DHED-treated 5xFAD mice. Finally, the reduction in synaptic proteins was found to also improve by treatment with cx-DHED. Therefore, we specifically demonstrated the protective effects of cx-DHED against AD pathologies and suggest that cx-DHED may be a potential therapeutic drug for AD.<\/jats:p>","DOI":"10.3390\/ijms231810602","type":"journal-article","created":{"date-parts":[[2022,9,13]],"date-time":"2022-09-13T21:06:52Z","timestamp":1663103212000},"page":"10602","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Effect of cx-DHED on Abnormal Glucose Transporter Expression Induced by AD Pathologies in the 5xFAD Mouse Model"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2631-5049","authenticated-orcid":false,"given":"Jinho","family":"Kim","sequence":"first","affiliation":[{"name":"Gachon Advanced Institute for Health Science and Technology, Graduate School, Gachon University, Incheon 21999, Korea"},{"name":"Neuroscience Research Institute, Gachon University, Incheon 21565, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"ShinWoo","family":"Kang","sequence":"additional","affiliation":[{"name":"Neuroscience Research Institute, Gachon University, Incheon 21565, Korea"},{"name":"Department of Pharmacology, College of Medicine, Gachon University, Incheon 21999, Korea"},{"name":"Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6157-6340","authenticated-orcid":false,"given":"Keun-A","family":"Chang","sequence":"additional","affiliation":[{"name":"Gachon Advanced Institute for Health Science and Technology, Graduate School, Gachon University, Incheon 21999, Korea"},{"name":"Neuroscience Research Institute, Gachon University, Incheon 21565, Korea"},{"name":"Department of Pharmacology, College of Medicine, Gachon University, Incheon 21999, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"311","DOI":"10.3233\/JAD-2010-1221","article-title":"Alzheimer\u2019s disease and the amyloid-\u03b2 peptide","volume":"19","author":"Murphy","year":"2010","journal-title":"J. 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