{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T17:48:38Z","timestamp":1790358518266,"version":"4.1.0"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,6,29]],"date-time":"2021-06-29T00:00:00Z","timestamp":1624924800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100015867","name":"Development of Innovative Strategies for a Transdisciplinary Approach to ALZheimer's Disease","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100015867","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001677","name":"Institut National de La Sant\u00e9 et de la Recherche M\u00e9dicale","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001677","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015872","name":"Universit\u00e9 de Lille","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100015872","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de La Recherche","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>\n                    Identifying which among several\n                    <jats:italic>in cellulo<\/jats:italic>\n                    pharmacological activities is necessary for the proper\n                    <jats:italic>in vivo<\/jats:italic>\n                    activity is essential for further drug development against Alzheimer\u2019s disease pathophysiological processes. An in-depth structure\u2013activity relationship\u2013based study has been carried out, and two molecules, named MAGS02-14 and PEL24-199, that share a \u00df-secretase modulatory effect associated or not to a lysosomotropic activity in cellulo have been identified. In terms of chemical formulas, MAGS02-14 and PEL24-199 only differ from each other by a single nitrogen atom. The study aimed to elucidate the\n                    <jats:italic>in vivo<\/jats:italic>\n                    pharmacological effects of lysosomotropic and\/or the \u00df-secretase modulatory activity in a tau pathology mouse model. To address this question, the THY-Tau22 transgenic model of tauopathy was treated with both compounds for 6\u00a0weeks in a curative paradigm. Short-term memory, tau burden, and inflammatory processes were analyzed using orthogonal methods, and PEL24-199, but not MAGS02-14, was shown to restore the short-term memory and reduce the neurofibrillary degenerating process. These effects were associated with a reduced phosphorylation of tau, an increased phosphatase expression, and decreased astrogliosis. Our results, therefore, suggest that the lysosomotropic activity may be nonessential for the effect on tau pathology.\n                  <\/jats:p>","DOI":"10.3389\/fphar.2021.679335","type":"journal-article","created":{"date-parts":[[2021,6,29]],"date-time":"2021-06-29T02:51:33Z","timestamp":1624935093000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["A \u00df-Secretase Modulator Decreases Tau Pathology and Preserves Short-Term Memory in a Mouse Model of Neurofibrillary Degeneration"],"prefix":"10.3389","volume":"12","author":[{"given":"Marie","family":"Tautou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabiha","family":"Eddarkaoui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Descamps","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul-Emmanuel","family":"Larchanch\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamal","family":"El Bakali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liesel Mary","family":"Goveas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00e9lanie","family":"Dumoulin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chlo\u00e9","family":"Lamarre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Blum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luc","family":"Bu\u00e9e","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Melnyk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Sergeant","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,6,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1186\/1750-1326-7-46","article-title":"Identification of BACE2 as an Avid SS-Amyloid-Degrading Protease","volume":"7","author":"Abdul-Hay","year":"2012","journal-title":"Mol. 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