{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:13:57Z","timestamp":1791918837275,"version":"4.3.4"},"reference-count":54,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,5,24]],"date-time":"2022-05-24T00:00:00Z","timestamp":1653350400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Warner\/Fermaturo and A. T. Still University Board of Trustees Research","award":["560-740"],"award-info":[{"award-number":["560-740"]}]},{"name":"A. T. Still University","award":["560-740"],"award-info":[{"award-number":["560-740"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Deposition of fibrillar forms of amyloid \u03b2-protein (A\u03b2) is commonly found in patients with Alzheimer\u2019s disease (AD) associated with cognitive decline. Impaired clearance of A\u03b2 species is thought to be a major cause of late-onset sporadic AD. A\u03b2 secreted into the extracellular milieu can be cleared from the brain through multiple pathways, including cellular uptake in neuronal and non-neuronal cells. Recent studies have showed that the naturally-occurring polyphenol amentoflavone (AMF) exerts anti-amyloidogenic effects. However, its effects on metabolism and cellular clearance of A\u03b2 remain to be tested. In the present study, we demonstrated that AMF significantly increased the cellular uptake of both A\u03b21-40 and A\u03b21-42, but not inverted A\u03b242-1 in mouse neuronal N2a cells. Though AMF promoted internalization of cytotoxic A\u03b21-42, it significantly reduced cell death in our assay condition. Our data further revealed that the internalized A\u03b2 is translocated to lysosomes and undergoes enzymatic degradation. The saturable kinetic of A\u03b2 uptake and our pharmacologic experiments showed the involvement of receptor-mediated endocytosis, in part, through the class A scavenger receptors as a possible mechanism of action of AMF. Taken together, our findings indicate that AMF can lower the levels of extracellular A\u03b2 by increasing their cellular uptake and clearance, suggesting the therapeutic potential of AMF for the treatment of AD.<\/jats:p>","DOI":"10.3390\/ijms23115885","type":"journal-article","created":{"date-parts":[[2022,5,24]],"date-time":"2022-05-24T22:04:06Z","timestamp":1653429846000},"page":"5885","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Amentoflavone Promotes Cellular Uptake and Degradation of Amyloid-Beta in Neuronal Cells"],"prefix":"10.3390","volume":"23","author":[{"given":"Byung Hee","family":"Han","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Kirksville College of Osteopathic Medicine, A.T. Still University of Health Sciences, Kirksville, MO 63501, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brooke","family":"Cofell","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Kirksville College of Osteopathic Medicine, A.T. Still University of Health Sciences, Kirksville, MO 63501, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Everhart","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Kirksville College of Osteopathic Medicine, A.T. Still University of Health Sciences, Kirksville, MO 63501, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Courtney","family":"Humpal","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Kirksville College of Osteopathic Medicine, A.T. Still University of Health Sciences, Kirksville, MO 63501, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sam-Sik","family":"Kang","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Seoul National University, Seoul 08826, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4306-7024","authenticated-orcid":false,"given":"Sang Kook","family":"Lee","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Seoul National University, Seoul 08826, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeong Sook","family":"Kim-Han","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Kirksville College of Osteopathic Medicine, A.T. Still University of Health Sciences, Kirksville, MO 63501, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S185","DOI":"10.3233\/JAD-2012-129028","article-title":"Alzheimer\u2019s disease: Recent advances and future perspectives","volume":"33","author":"Ubhi","year":"2013","journal-title":"J. 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