{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T03:55:07Z","timestamp":1791863707184,"version":"4.3.4"},"reference-count":43,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2020,2,3]],"date-time":"2020-02-03T00:00:00Z","timestamp":1580688000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["KAKENHI Grant-in-Aid for Scientific Research (C) 16K08254"],"award-info":[{"award-number":["KAKENHI Grant-in-Aid for Scientific Research (C) 16K08254"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["KAKENHI Grant-in-Aid for Scientific Research (C) 19K07093"],"award-info":[{"award-number":["KAKENHI Grant-in-Aid for Scientific Research (C) 19K07093"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","award":["Strategic Research Foundation at Private Universities in Japan for years 2015-2019"],"award-info":[{"award-number":["Strategic Research Foundation at Private Universities in Japan for years 2015-2019"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Amyloid-\u03b2 (A\u03b2) peptides play a crucial role in the pathogenesis of Alzheimer\u2019s disease (AD). A\u03b2 production, aggregation, and clearance are thought to be important therapeutic targets for AD. Curcumin has been known to have an anti-amyloidogenic effect on AD. In the present study, we performed screening analysis using a curcumin derivative library with the aim of finding derivatives effective in suppressing A\u03b2 production with improved bioavailability of curcumin using CHO cells that stably express human amyloid-\u03b2 precursor protein and using human neuroblastoma SH-SY5Y cells. We found that the curcumin derivative GT863\/PE859, which has been shown to have an inhibitory effect on A\u03b2 and tau aggregation in vivo, was more effective than curcumin itself in reducing A\u03b2 secretion. We further found that GT863 inhibited neither \u03b2- nor \u03b3-secretase activity, but did suppress \u03b3-secretase-mediated cleavage in a substrate-dependent manner. We further found that GT863 suppressed N-linked glycosylation, including that of the \u03b3-secretase subunit nicastrin. We also found that mannosidase inhibitors that block the mannose trimming step of N-glycosylation suppressed A\u03b2 production in a similar fashion, as was observed as a result of treatment with GT863. Collectively, these results suggest that GT863 downregulates N-glycosylation, resulting in suppression of A\u03b2 production without affecting secretase activity.<\/jats:p>","DOI":"10.3390\/cells9020349","type":"journal-article","created":{"date-parts":[[2020,2,6]],"date-time":"2020-02-06T02:59:18Z","timestamp":1580957958000},"page":"349","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Curcumin Derivative GT863 Inhibits Amyloid-Beta Production via Inhibition of Protein N-Glycosylation"],"prefix":"10.3390","volume":"9","author":[{"given":"Yasuomi","family":"Urano","sequence":"first","affiliation":[{"name":"Department of Medical Life Systems, Faculty of Life and Medical Sciences, Doshisha University, 1\u20133 Miyakodani, Tatara, Kyotanabe, Kyoto 610 0394, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mina","family":"Takahachi","sequence":"additional","affiliation":[{"name":"Department of Medical Life Systems, Faculty of Life and Medical Sciences, Doshisha University, 1\u20133 Miyakodani, Tatara, Kyotanabe, Kyoto 610 0394, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryo","family":"Higashiura","sequence":"additional","affiliation":[{"name":"Department of Medical Life Systems, Faculty of Life and Medical Sciences, Doshisha University, 1\u20133 Miyakodani, Tatara, Kyotanabe, Kyoto 610 0394, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hitomi","family":"Fujiwara","sequence":"additional","affiliation":[{"name":"Department of Medical Life Systems, Faculty of Life and Medical Sciences, Doshisha University, 1\u20133 Miyakodani, Tatara, Kyotanabe, Kyoto 610 0394, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoru","family":"Funamoto","sequence":"additional","affiliation":[{"name":"Department of Medical Life Systems, Faculty of Life and Medical Sciences, Doshisha University, 1\u20133 Miyakodani, Tatara, Kyotanabe, Kyoto 610 0394, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"So","family":"Imai","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cell Biology, Graduate School of Agricultural Science, Tohoku University, 468-1 Aramakiazaaoba, Aobaku, Sendai, Miyagi 980-0845, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugene","family":"Futai","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cell Biology, Graduate School of Agricultural Science, Tohoku University, 468-1 Aramakiazaaoba, Aobaku, Sendai, Miyagi 980-0845, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0211-7144","authenticated-orcid":false,"given":"Michiaki","family":"Okuda","sequence":"additional","affiliation":[{"name":"Green Tech Co., Ltd., 1\u20137\u20137 Yaesu, Chuo-ku, Tokyo 103-0028, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hachiro","family":"Sugimoto","sequence":"additional","affiliation":[{"name":"Department of Medical Life Systems, Faculty of Life and Medical Sciences, Doshisha University, 1\u20133 Miyakodani, Tatara, Kyotanabe, Kyoto 610 0394, Japan"},{"name":"Green Tech Co., Ltd., 1\u20137\u20137 Yaesu, Chuo-ku, Tokyo 103-0028, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noriko","family":"Noguchi","sequence":"additional","affiliation":[{"name":"Department of Medical Life Systems, Faculty of Life and Medical Sciences, Doshisha University, 1\u20133 Miyakodani, Tatara, Kyotanabe, Kyoto 610 0394, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,2,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1126\/science.1074069","article-title":"Alzheimer\u2019s disease is a synaptic failure","volume":"298","author":"Selkoe","year":"2002","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"29615","DOI":"10.1074\/jbc.R800019200","article-title":"Amyloid precursor protein trafficking, processing, and function","volume":"283","author":"Thinakaran","year":"2008","journal-title":"J. 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