{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T08:48:46Z","timestamp":1790844526982,"version":"4.1.0"},"reference-count":39,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2016,9,9]],"date-time":"2016-09-09T00:00:00Z","timestamp":1473379200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81202200"],"award-info":[{"award-number":["81202200"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81130053"],"award-info":[{"award-number":["81130053"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) is the most common type of dementia. Amyloid-\u03b2 protein (A\u03b2) is identified as the core protein of neuritic plaques. A\u03b2 is generated by the sequential cleavage of the amyloid precursor protein (APP) via the APP cleaving enzyme (\u03b1-secretase, or \u03b2-secretase) and \u03b3-secretase. Previous studies indicated that folate deficiency elevated A\u03b2 deposition in APP\/PS1 mice, and this rise was prevented by folic acid. In the present study, we aimed to investigate whether folic acid could influence the generation of A\u03b2 by regulating \u03b1-, \u03b2-, and \u03b3-secretase. Herein, we demonstrated that folic acid reduced the deposition of A\u03b242 in APP\/PS1 mice brain by decreasing the mRNA and protein expressions of \u03b2-secretase [beta-site APP-cleaving enzyme 1 (BACE1)] and \u03b3-secretase complex catalytic component\u2014presenilin 1 (PS1)\u2014in APP\/PS1 mice brain. Meanwhile, folic acid increased the levels of ADAM9 and ADAM10, which are important \u03b1-secretases in ADAM (a disintegrin and metalloprotease) family. However, folic acid has no impact on the protein expression of nicastrin (Nct), another component of \u03b3-secretase complex. Moreover, folic acid regulated the expression of miR-126-3p and miR-339-5p, which target ADAM9 and BACE1, respectively. Taken together, the effect of folic acid on A\u03b2 deposition may relate to making APP metabolism through non-amyloidogenic pathway by decreasing \u03b2-secretase and increasing \u03b1-secretase. MicroRNA (miRNA) may involve in the regulation mechanism of folic acid on secretase expression.<\/jats:p>","DOI":"10.3390\/nu8090556","type":"journal-article","created":{"date-parts":[[2016,9,9]],"date-time":"2016-09-09T10:36:06Z","timestamp":1473417366000},"page":"556","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Effects of Folic Acid on Secretases Involved in A\u03b2 Deposition in APP\/PS1 Mice"],"prefix":"10.3390","volume":"8","author":[{"given":"Tian","family":"Tian","sequence":"first","affiliation":[{"name":"Department of Nutrition and Food Science, School of Public Health, Tianjin Medical University, Tianjin 300070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong","family":"Bai","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Science, School of Public Health, Tianjin Medical University, Tianjin 300070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Science, School of Public Health, Tianjin Medical University, Tianjin 300070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guo-Wei","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Science, School of Public Health, Tianjin Medical University, Tianjin 300070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Science, School of Public Health, Tianjin Medical University, Tianjin 300070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2016,9,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4245","DOI":"10.1073\/pnas.82.12.4245","article-title":"Amyloid plaque core protein in Alzheimer disease and Downsyndrome","volume":"82","author":"Masters","year":"1985","journal-title":"Proc. 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