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(NRF) grant funded by the Korea Government (MEST)","award":["24-BR-03-05"],"award-info":[{"award-number":["24-BR-03-05"]}]},{"name":"National Research Foundation of Korea (NRF) grant funded by the Korea Government (MEST)","award":["23YR1600"],"award-info":[{"award-number":["23YR1600"]}]},{"name":"National Research Foundation of Korea (NRF) grant funded by the Korea Government (MEST)","award":["RS-2024-00342397"],"award-info":[{"award-number":["RS-2024-00342397"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Most approved drugs for Alzheimer\u2019s disease (AD) are indicated for early to moderate stages and primarily target amyloid-beta or neurotransmitter systems. While these treatments may slow cognitive decline, they do not halt disease progression and are often limited by high cost and modest efficacy. Natural compounds are increasingly being explored as alternative interventions. Our previous study showed that oral administration of Avenanthramide-C (Avn-C), a natural polyphenol from oats, for 14 days from early AD stages improved cognition and reduced neuroinflammation in AD mice. To assess its long-term potential, in this study we extended Avn-C treatment to three months starting from early disease stages in 5xFAD and Tg2576 models. Sustained administration preserved recovered long-term potentiation (LTP) by maintaining AMPK activation and inhibiting caspase-3 and GSK3\u03b2, thereby reducing amyloid accumulation and tau hyperphosphorylation in the hippocampus. Avn-C also maintained anti-inflammatory effects by suppressing NF-\u03baB-mediated proinflammatory cytokine release and preventing chronic microglial activation. This promoted microglial coverage of plaques in vivo and enhanced phagocytosis in vitro. Our findings suggest that early and sustained Avn-C treatment preserves cognitive function, modulates multiple pathological pathways, and may slow or prevent AD progression by targeting early neurodegenerative processes before irreversible damage occurs.<\/jats:p>","DOI":"10.3390\/cells14110826","type":"journal-article","created":{"date-parts":[[2025,6,2]],"date-time":"2025-06-02T12:27:09Z","timestamp":1748867229000},"page":"826","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Avenanthramide-C as Alzheimer\u2019s Disease-Modifying Therapy: Early and Sustained Intervention Prevents Disease Progression in Mouse Models"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-8690-914X","authenticated-orcid":false,"given":"Alen Benhur Pravin","family":"Nathan","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, Chonnam National University Medical School, Gwangju 61469, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8726-6789","authenticated-orcid":false,"given":"Areeba","family":"Aziz","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Chonnam National University Medical School, Gwangju 61469, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0431-9185","authenticated-orcid":false,"given":"Semyeong","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Medicinal Biotechnology, College of Health Sciences, Dong-A University, Busan 49236, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seunghee","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Chonnam National University Medical School, Gwangju 61469, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seyoung","family":"Jeon","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Chonnam National University Medical School, Gwangju 61469, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8297-9747","authenticated-orcid":false,"given":"Hyung-Seok","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Forensic Medicine, Chonnam National University Medical School, Gwangju 58128, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0995-6952","authenticated-orcid":false,"given":"Jonghyun","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Medicinal Biotechnology, College of Health Sciences, Dong-A University, Busan 49236, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jihoon","family":"Jo","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Chonnam National University Medical School, Gwangju 61469, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1007\/BF01108841","article-title":"Memory deficits in Alzheimer\u2019s patients: A comprehensive review","volume":"3","author":"Carlesimo","year":"1992","journal-title":"Neuropsychol. 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