{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T19:41:59Z","timestamp":1783453319442,"version":"3.55.0"},"reference-count":47,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2016,7,13]],"date-time":"2016-07-13T00:00:00Z","timestamp":1468368000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,7,13]],"date-time":"2016-07-13T00:00:00Z","timestamp":1468368000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Neprilysin (NEP) is the most important A\u03b2-degrading enzyme. Its expression level decreases with age and inversely correlated with amyloid accumulation, suggesting its correlation with the late-onset of Alzheimer\u2019s disease. Recently, many reports showed that upregulating NEP level is a promising strategy in the prevention and therapy of Alzheimer\u2019s disease. Here, we used a sensitive fluorescence-based A\u03b2 digestion assay to screen 25 curcumin analogs for their ability to upregulate NEP activity. To our surprise, four compounds, dihydroxylated curcumin, monohydroxylated demethoxycurcumin and mono- and di-hydroxylated bisdemethoxycurcumin, increased NEP activity, while curcumin did not. The ability of these polyhydroxycurcuminoids to upregulate NEP was further confirmed by mRNA and protein expression levels in the cell and mouse models. Finally, feeding monohydroxylated demethoxycurcumin (also named demethylcurcumin) or dihydroxylated bisdemethoxycurcumin (also named bisdemethylcurcumin) to APP\n                    <jats:sub>swe<\/jats:sub>\n                    \/PS\n                    <jats:sub>1<\/jats:sub>\n                    dE\n                    <jats:sub>9<\/jats:sub>\n                    double transgenic mice upregulated NEP levels in the brain and reduced A\u03b2 accumulation in the hippocampus and cortex. These polyhydroxycurcuminoids offer hope in the prevention of Alzheimer\u2019s disease.\n                  <\/jats:p>","DOI":"10.1038\/srep29760","type":"journal-article","created":{"date-parts":[[2016,7,13]],"date-time":"2016-07-13T06:03:51Z","timestamp":1468389831000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Polyhydroxycurcuminoids but not curcumin upregulate neprilysin and can be applied to the prevention of Alzheimer\u2019s disease"],"prefix":"10.1038","volume":"6","author":[{"given":"Po-Ting","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zih-ten","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Chi","family":"Hou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lung-Chih","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rita P.-Y.","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,7,13]]},"reference":[{"key":"BFsrep29760_CR1","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/alzrt246","volume":"6","author":"L Lannfelt","year":"2014","unstructured":"Lannfelt, L. et al. 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