{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T05:30:20Z","timestamp":1768455020526,"version":"3.49.0"},"reference-count":46,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T00:00:00Z","timestamp":1649808000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"KOREA RESEARCH FOUNDATION GRANT","award":["2017-0919"],"award-info":[{"award-number":["2017-0919"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>\u03b2-Amyloid (A\u03b2) is a hallmark peptide of Alzheimer\u2019s disease (AD). Herein, we explored the mechanism underlying the cytotoxicity of this peptide. Double treatment with oligomeric 42-amino-acid A\u03b2 (A\u03b242) species, which are more cytotoxic than other conformers such as monomers and fibrils, resulted in increased cytotoxicity. Under this treatment condition, an increase in intracellular localization of the peptide was observed, which indicated that the peptide administered extracellularly entered the cells. The cell-permeable peptide TAT-tagged A\u03b242 (tA\u03b242), which was newly prepared for the study and found to be highly cell-permeable and soluble, induced A\u03b2-specific lamin protein cleavage, caspase-3\/7-like DEVDase activation, and high cytotoxicity (5\u201310-fold higher than that induced by the wild-type oligomeric preparations). Oligomeric species enrichment and double treatment were not necessary for enhancing the cytotoxicity and intracellular location of the fusion peptide. Taiwaniaflavone, an inhibitor of the cytotoxicity of wild-type A\u03b242 and tA\u03b242, strongly blocked the internalization of the peptides into the cells. These data imply a strong relationship between the cytotoxicity and intracellular location of the A\u03b2 peptide. Based on these results, we suggest that agents that can reduce the cell permeability of A\u03b242 are potential AD therapeutics.<\/jats:p>","DOI":"10.3390\/life12040577","type":"journal-article","created":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T21:33:42Z","timestamp":1649885622000},"page":"577","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Evidence for a Strong Relationship between the Cytotoxicity and Intracellular Location of \u03b2-Amyloid"],"prefix":"10.3390","volume":"12","author":[{"given":"Md. Aminul","family":"Haque","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, Chosun University, Gwangju 61452, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Md. Selim","family":"Hossain","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Chosun University, Gwangju 61452, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tahmina","family":"Bilkis","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Chosun University, Gwangju 61452, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3126-5453","authenticated-orcid":false,"given":"Md. Imamul","family":"Islam","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Chosun University, Gwangju 61452, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4754-6142","authenticated-orcid":false,"given":"Il-Seon","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Chosun University, Gwangju 61452, Korea"},{"name":"Department of Cellular and Molecular Medicine, Chosun University, Gwangju 61452, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"221","DOI":"10.3389\/fphar.2015.00221","article-title":"beta-Amyloid: The key peptide in the pathogenesis of Alzheimer\u2019s disease","volume":"6","author":"Sun","year":"2015","journal-title":"Front. 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