{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T00:27:31Z","timestamp":1779323251817,"version":"3.51.4"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,6,7]],"date-time":"2024-06-07T00:00:00Z","timestamp":1717718400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2022R1A2C100425612"],"award-info":[{"award-number":["2022R1A2C100425612"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2022R1A4A2000767"],"award-info":[{"award-number":["2022R1A4A2000767"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"<jats:p>Excessive accumulation of amyloid-\u03b2 (A\u03b2) has been associated with the pathogenesis of Alzheimer\u2019s disease (AD). Clinical studies have further proven that elimination of A\u03b2 can be a viable therapeutic option. In the current study, we conceptualized a fusion membrane protein, referred to as synthetic \u03b1-secretase (SAS), that can cleave amyloid precursor protein (APP) and A\u03b2 specifically at the \u03b1-site. In mammalian cells, SAS indeed cleaved APP and A\u03b2 at the \u03b1-site. Overexpression of SAS in the hippocampus was achieved by direct injection of recombinant adeno-associated virus serotype 9 (AAV9) that expresses SAS (AAV9-SAS) into the bilateral ventricles of mouse brains. SAS enhanced the non-amyloidogenic processing of APP, thus reducing the levels of soluble A\u03b2 and plaques in the 5xFAD mice. In addition, SAS significantly attenuated the cognitive deficits in 5xFAD mice, as demonstrated by novel object recognition and Morris water maze tests. Unlike other A\u03b2-cleaving proteases, SAS has highly strict substrate specificity. We propose that SAS can be an efficient modality to eliminate excessive A\u03b2 from diseased brains.<\/jats:p>","DOI":"10.3389\/fnagi.2024.1383905","type":"journal-article","created":{"date-parts":[[2024,6,11]],"date-time":"2024-06-11T18:57:05Z","timestamp":1718132225000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Therapeutic effects of a novel synthetic \u03b1-secretase"],"prefix":"10.3389","volume":"16","author":[{"given":"Sung Bin","family":"Kim","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bo-Ram","family":"Mun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sung Yoon","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muthukumar","family":"Elangovan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Euy Jun","family":"Park","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Won-Seok","family":"Choi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Woo Jin","family":"Park","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2024,6,7]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"4277","DOI":"10.1523\/jneurosci.5078-05.2006","article-title":"\u03b2-amyloid accumulation impairs multivesicular body sorting by inhibiting the ubiquitin-proteasome system","volume":"26","author":"Almeida","year":"2006","journal-title":"J. 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