{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:07:26Z","timestamp":1785434846555,"version":"3.56.0"},"reference-count":40,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T00:00:00Z","timestamp":1782345600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Ministry of Health & Welfare, Republic of Korea","award":["RS-2022-KH130303"],"award-info":[{"award-number":["RS-2022-KH130303"]}]},{"name":"the Ministry of Health & Welfare, Republic of Korea","award":["RS-2021-KH113820"],"award-info":[{"award-number":["RS-2021-KH113820"]}]},{"name":"the Ministry of Health & Welfare, Republic of Korea","award":["RS-2025-25303051"],"award-info":[{"award-number":["RS-2025-25303051"]}]},{"award":["RS-2022-KH130303"],"award-info":[{"award-number":["RS-2022-KH130303"]}],"id":[{"id":"https:\/\/ror.org\/00vxgjw72","id-type":"ROR","asserted-by":"publisher"}]},{"award":["RS-2021-KH113820"],"award-info":[{"award-number":["RS-2021-KH113820"]}],"id":[{"id":"https:\/\/ror.org\/00vxgjw72","id-type":"ROR","asserted-by":"publisher"}]},{"award":["RS-2025-25303051"],"award-info":[{"award-number":["RS-2025-25303051"]}],"id":[{"id":"https:\/\/ror.org\/00vxgjw72","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Preventing or reversing Tau hyperphosphorylation and aggregation represent critical objectives in the development of effective therapies for Alzheimer\u2019s disease. The present study investigated the potential of a novel Aronia bioactive fraction\u2014alginic acid nanocomplex (AANCP)\u2014to simultaneously inhibit pathological features of Alzheimer\u2019s disease. Evaluations of Aronia bioactive fraction (ABF) and low-molecular-weight alginic acid (LAA), utilized both individually and as AANCP, were conducted in HEK293-TauP301L and SH-SY5Y-TauP301L cell models of Alzheimer\u2019s disease. Both ABF and LAA reduced the expression of total Tau and Tau phosphorylated at Ser396 in a concentration-dependent manner, with AANCP demonstrating significant synergistic activity of its components. Notably, the optimal AANCP ratio was 1:1 and 1:8 for inhibiting Tau phosphorylation and Tau aggregation, respectively. Mechanistically, AANCP inhibited Tau phosphorylation by upregulating p-Akt (phosphorylated protein kinase B) and p-GSK-3\u03b2 (phosphorylated glycogen synthase kinase-3 beta), while also enhancing the activity of methylated PP2A, a key Tau phosphatase. Furthermore, AANCP exhibited superior efficacy in inhibiting heparin-induced Tau aggregation compared to the individual components. Analysis of autophagy markers indicated that the nanocomplex enhanced Tau clearance, as shown by increased LC3-II and Beclin-1 levels and reduced p62 levels. These results suggest AANCP as a promising therapeutic candidate that simultaneously reduces Tau phosphorylation and aggregation and facilitates autophagic Tau clearance, offering a potent, synergistic strategy for treating Alzheimer\u2019s disease.<\/jats:p>","DOI":"10.3390\/ijms27135748","type":"journal-article","created":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T00:49:23Z","timestamp":1782434963000},"page":"5748","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Aronia Bioactive Fraction-Alginic Acid Nanocomplex-Modulates Tau Phosphorylation and Aggregation in Cell Models of Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"27","author":[{"given":"Hye-Yeon","family":"Kang","sequence":"first","affiliation":[{"name":"JBKLAB, Inc., 17 Techno 4-ro, Yuseoung-gu, Daejeon 34013, Republic of Korea"},{"name":"Department of Medical Genetics, Ajou University School of Medicine, Suwon 16499, Republic of Korea"},{"name":"BK21 R&E Initiative for Advanced Precision Medicine, Department of Biomedical Sciences, Graduate School of Ajou University, Suwon 16499, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bong-Keun","family":"Jang","sequence":"additional","affiliation":[{"name":"JBKLAB, Inc., 17 Techno 4-ro, Yuseoung-gu, Daejeon 34013, Republic of Korea"},{"name":"Department of Herbology, College of Korean Medicine, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6197-1383","authenticated-orcid":false,"given":"Seong-Hoon","family":"Yun","sequence":"additional","affiliation":[{"name":"JBKLAB, Inc., 17 Techno 4-ro, Yuseoung-gu, Daejeon 34013, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hee-Yeong","family":"Jeong","sequence":"additional","affiliation":[{"name":"JBKLAB, Inc., 17 Techno 4-ro, Yuseoung-gu, Daejeon 34013, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1928-5531","authenticated-orcid":false,"given":"Eunkuk","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Ajou University School of Medicine, Suwon 16499, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7787-7394","authenticated-orcid":false,"given":"Kang-Il","family":"Oh","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Ajou University School of Medicine, Suwon 16499, Republic of Korea"},{"name":"BK21 R&E Initiative for Advanced Precision Medicine, Department of Biomedical Sciences, Graduate School of Ajou University, Suwon 16499, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-5871-2656","authenticated-orcid":false,"given":"Junhwan","family":"Jeong","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Ajou University School of Medicine, Suwon 16499, Republic of Korea"},{"name":"BK21 R&E Initiative for Advanced Precision Medicine, Department of Biomedical Sciences, Graduate School of Ajou University, Suwon 16499, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0625-3530","authenticated-orcid":false,"given":"Seon-Yong","family":"Jeong","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Ajou University School of Medicine, Suwon 16499, Republic of Korea"},{"name":"BK21 R&E Initiative for Advanced Precision Medicine, Department of Biomedical Sciences, Graduate School of Ajou University, Suwon 16499, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1038\/s41582-018-0013-z","article-title":"Tau-targeting therapies for Alzheimer disease","volume":"14","author":"Congdon","year":"2018","journal-title":"Nat. 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