{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T16:54:12Z","timestamp":1787849652759,"version":"build-2784847793"},"reference-count":65,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2021,6,18]],"date-time":"2021-06-18T00:00:00Z","timestamp":1623974400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Samford University","award":["Faculty Development Grant"],"award-info":[{"award-number":["Faculty Development Grant"]}]},{"name":"McWhorter School of Pharmacy-Samford University","award":["Dean's Innovation Grant"],"award-info":[{"award-number":["Dean's Innovation Grant"]}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21AG063197"],"award-info":[{"award-number":["R21AG063197"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathophysiology"],"abstract":"<jats:p>The use of angiotensin-converting enzyme inhibitors (ACEis) has been reported to reduce symptoms of cognitive decline in patients with Alzheimer\u2019s disease (AD). Yet, the protective role of ACEis against AD symptoms is still controversial.\u00a0Here, we aimed at determining whether oral treatment with the ACEi lisinopril has beneficial effects on cognitive and physical functions in a Drosophila melanogaster model of AD that overexpresses the human amyloid precursor protein and the human \u03b2-site APP-cleaving enzyme in neurons. We found a significant impairment in learning and memory as well as in climbing ability in young AD flies compared to control flies. After evaluation of the kynurenine pathway of tryptophan metabolism, we also found that AD flies displayed a &gt;30-fold increase in the levels of the neurotoxic 3-hydroxykynurenine (3-HK) in their heads. Furthermore, compared to control flies, AD flies had significantly higher levels of the reactive oxygen species (ROS) hydrogen peroxide in their muscle-enriched thoraces. Lisinopril significantly improved deficits in learning and memory and climbing ability in AD flies. The positive impact of lisinopril on physical function might be, in part, explained by a significant reduction in ROS levels in the thoraces of the lisinopril-fed AD flies. However, lisinopril did not affect the levels of 3-HK. In conclusion, our findings provide novel and relevant insights into the therapeutic potential of ACEis in a preclinical AD model.<\/jats:p>","DOI":"10.3390\/pathophysiology28020020","type":"journal-article","created":{"date-parts":[[2021,6,20]],"date-time":"2021-06-20T21:50:15Z","timestamp":1624225815000},"page":"307-319","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["The Angiotensin-Converting Enzyme Inhibitor Lisinopril Mitigates Memory and Motor Deficits in a Drosophila Model of Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"28","author":[{"given":"Jimiece","family":"Thomas","sequence":"first","affiliation":[{"name":"McWhorter School of Pharmacy, Samford University, Birmingham, AL 35229, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haddon","family":"Smith","sequence":"additional","affiliation":[{"name":"McWhorter School of Pharmacy, Samford University, Birmingham, AL 35229, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. Aaron","family":"Smith","sequence":"additional","affiliation":[{"name":"McWhorter School of Pharmacy, Samford University, Birmingham, AL 35229, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lori","family":"Coward","sequence":"additional","affiliation":[{"name":"Pharmaceutical Sciences Research Institute, McWhorter School of Pharmacy, Samford University, Birmingham, AL 35229, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory","family":"Gorman","sequence":"additional","affiliation":[{"name":"Pharmaceutical Sciences Research Institute, McWhorter School of Pharmacy, Samford University, Birmingham, AL 35229, USA"},{"name":"Pharmaceutical, Social, and Administrative Sciences, McWhorter School of Pharmacy, Samford University, Birmingham, AL 35229, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6345-7508","authenticated-orcid":false,"given":"Maria","family":"De Luca","sequence":"additional","affiliation":[{"name":"Department of Nutrition Sciences, School of Health Professions, University of Alabama, Birmingham, AL 35233, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Jumbo-Lucioni","sequence":"additional","affiliation":[{"name":"Pharmaceutical, Social, and Administrative Sciences, McWhorter School of Pharmacy, Samford University, Birmingham, AL 35229, USA"},{"name":"Department of Biology, College of Arts and Sciences, University of Alabama, Birmingham, AL 35233, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1016\/S0140-6736(16)32381-9","article-title":"Future life expectancy in 35 industrialised countries: Projections with a Bayesian model ensemble","volume":"389","author":"Kontis","year":"2017","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.jalz.2010.11.002","article-title":"Trends in the incidence and prevalence of Alzheimer\u2019s disease, dementia, and cognitive impairment in the United States","volume":"7","author":"Rocca","year":"2011","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"(2020). 2020 Alzheimer\u2019s disease facts and figures. 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