{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T06:45:56Z","timestamp":1776840356944,"version":"3.51.2"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T00:00:00Z","timestamp":1776816000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"<jats:p>Alzheimer\u2019s disease (AD), the leading cause of dementia, is characterized by extracellular amyloid-\u03b2 (A\u03b2) accumulation. Immunotherapies targeting A\u03b2 clearance show promise, highlighting the therapeutic value of enhancing A\u03b2 removal. We previously identified that nuclear inclusion a (NIa), a plant viral protease, fortuitously cleaves A\u03b2 with strict sequence specificity. Here, we engineered a secretory form, SecNIa, to degrade extracellular A\u03b2. SecNIa was efficiently secreted from transfected cells while retaining potent A\u03b2-cleaving activity. Adeno-associated virus (AAV)-mediated delivery of SecNIa into 5xFAD mice resulted in robust hippocampal expression and cerebrospinal fluid secretion. SecNIa expression significantly reduced soluble and insoluble A\u03b2, decreased hippocampal plaques, and improved cognition, fully normalizing recognition memory and enhancing spatial learning. These findings establish SecNIa as a promising therapeutic strategy to directly target pathogenic extracellular A\u03b2 in AD.<\/jats:p>","DOI":"10.3389\/fnagi.2026.1720518","type":"journal-article","created":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T05:48:16Z","timestamp":1776836896000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Secretory form of viral protease NIa ameliorates amyloid-\u03b2 pathology and cognitive deficits in a mouse model of Alzheimer\u2019s disease"],"prefix":"10.3389","volume":"18","author":[{"given":"Euy Jun","family":"Park","sequence":"first","affiliation":[{"name":"School of Life Sciences, Gwangju Institute of Science and Technology","place":["Gwangju, Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bo-Ram","family":"Mun","sequence":"additional","affiliation":[{"name":"School of Biological Sciences and Technology, Chonnam National University","place":["Gwangju, Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sung Yoon","family":"Kim","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Gwangju Institute of Science and Technology","place":["Gwangju, Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muthukumar","family":"Elangovan","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Gwangju Institute of Science and Technology","place":["Gwangju, Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sung Bin","family":"Kim","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Gwangju Institute of Science and Technology","place":["Gwangju, Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Won-Seok","family":"Choi","sequence":"additional","affiliation":[{"name":"School of Biological Sciences and Technology, Chonnam National University","place":["Gwangju, Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Woo Jin","family":"Park","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Gwangju Institute of Science and Technology","place":["Gwangju, Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,22]]},"reference":[{"key":"B1","unstructured":"Dementia Statistics.\n          \n          2024"},{"key":"B2","doi-asserted-by":"publisher","first-page":"2613","DOI":"10.1002\/(SICI)1521-4141(199908)29:08<2613::AID-IMMU2613>3.0.CO;2-J","article-title":"Recombinant human IgG molecules lacking Fc\u03b3 receptor I binding and monocyte triggering activities.","volume":"29","author":"Armour","year":"1999","journal-title":"Eur. 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