{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T13:06:25Z","timestamp":1768741585724,"version":"3.49.0"},"reference-count":41,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,4,27]],"date-time":"2023-04-27T00:00:00Z","timestamp":1682553600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Muscular Dystrophy Association Cyprus\/Telethon Cyprus","award":["33173180"],"award-info":[{"award-number":["33173180"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) is a progressive neurodegenerative disease and is the most common type of dementia. Although a considerably large amount of money has been invested in drug development for AD, no disease modifying treatment has been detected so far. In our previous work, we developed a computational method to highlight stage-specific candidate repurposed drugs against AD. In this study, we tested the effect of the top 13 candidate repurposed drugs that we proposed in our previous work in a severity stage-specific manner using an in vitro BACE1 assay and the effect of a top-ranked drug from the list of our previous work, tetrabenazine (TBZ), in the 5XFAD as an AD mouse model. From our in vitro screening, we detected 2 compounds (clomiphene citrate and Pik-90) that showed statistically significant inhibition against the activity of the BACE1 enzyme. The administration of TBZ at the selected dose and therapeutic regimen in 5XFAD in male and female mice showed no significant effect in behavioral tests using the Y-maze and the ELISA immunoassay of A\u03b240. To our knowledge, this is the first time the drug tetrabenazine has been tested in the 5XFAD mouse model of AD in a sex-stratified manner. Our results highlight 2 drugs (clomiphene citrate and Pik-90) from our previous computational work for further investigation.<\/jats:p>","DOI":"10.3390\/life13051095","type":"journal-article","created":{"date-parts":[[2023,4,28]],"date-time":"2023-04-28T01:33:40Z","timestamp":1682645620000},"page":"1095","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Preliminary In Vitro and In Vivo Insights of In Silico Candidate Repurposed Drugs for Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"13","author":[{"given":"Kyriaki","family":"Savva","sequence":"first","affiliation":[{"name":"Bioinformatics Department, The Cyprus Institute of Neurology and Genetics, 2371 Nicosia, Cyprus"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8950-4077","authenticated-orcid":false,"given":"Margarita","family":"Zachariou","sequence":"additional","affiliation":[{"name":"Bioinformatics Department, The Cyprus Institute of Neurology and Genetics, 2371 Nicosia, Cyprus"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1914-1340","authenticated-orcid":false,"given":"Demos","family":"Kynigopoulos","sequence":"additional","affiliation":[{"name":"Department of Neuropathology, The Cyprus Institute of Neurology and Genetics, 2371 Nicosia, Cyprus"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eleni","family":"Fella","sequence":"additional","affiliation":[{"name":"Department of Neuropathology, The Cyprus Institute of Neurology and Genetics, 2371 Nicosia, Cyprus"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria-Ioanna","family":"Vitali","sequence":"additional","affiliation":[{"name":"Experimental Pharmacology Laboratory, Medical School, University of Cyprus, 2109 Nicosia, Cyprus"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xeni","family":"Kosofidou","sequence":"additional","affiliation":[{"name":"Experimental Pharmacology Laboratory, Medical School, University of Cyprus, 2109 Nicosia, Cyprus"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-9238-586X","authenticated-orcid":false,"given":"Michail","family":"Spyrou","sequence":"additional","affiliation":[{"name":"Experimental Pharmacology Laboratory, Medical School, University of Cyprus, 2109 Nicosia, Cyprus"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5143-0823","authenticated-orcid":false,"given":"Irene","family":"Sargiannidou","sequence":"additional","affiliation":[{"name":"Neuroscience Department, The Cyprus Institute of Neurology and Genetics, 2371 Nicosia, Cyprus"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Panayiotou","sequence":"additional","affiliation":[{"name":"Department of Neuropathology, The Cyprus Institute of Neurology and Genetics, 2371 Nicosia, Cyprus"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8365-3837","authenticated-orcid":false,"given":"Nikolas","family":"Dietis","sequence":"additional","affiliation":[{"name":"Experimental Pharmacology Laboratory, Medical School, University of Cyprus, 2109 Nicosia, Cyprus"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2470-3363","authenticated-orcid":false,"given":"George M.","family":"Spyrou","sequence":"additional","affiliation":[{"name":"Bioinformatics Department, The Cyprus Institute of Neurology and Genetics, 2371 Nicosia, Cyprus"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/s40035-018-0107-y","article-title":"Alzheimer\u2019s disease hypothesis and related therapies","volume":"7","author":"Du","year":"2018","journal-title":"Transl. 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