{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:44:37Z","timestamp":1760035477687,"version":"build-2065373602"},"reference-count":38,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2025,7,8]],"date-time":"2025-07-08T00:00:00Z","timestamp":1751932800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Bulgarian National Science Fund","award":["KP-06-N63\/11","14.12.2022","IC-SK\/03\/2025-2026"],"award-info":[{"award-number":["KP-06-N63\/11","14.12.2022","IC-SK\/03\/2025-2026"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) is the most common cause of dementia in older adults and is becoming a major public health crisis as life expectancy increases worldwide. A major contributor to this disease is a deficiency in melatonin signaling. We have recently synthesised a series of melatonin analogs containing donepezil fragments. These compounds have been tested both in silico and in vitro. In this study, a particularly potent compound, 3a, was evaluated in a hybrid rat model of melatonin deficiency and AD. Rats underwent pinealectomy followed one week later by bilateral intracerebroventricular infusion of A\u03b21-42 (1 \u00b5g\/\u00b5L). A 14-day subchronic treatment with compound 3a was started simultaneously with the neurotoxin infusion. Melatonin was used as a reference drug, while a matched sham group received vehicle treatment. One week after the A\u03b21-42 infusion, the rats\u2019 cognitive functions were assessed using two Y-maze protocols, object recognition and object location tests. Markers of oxidative stress, including hippocampal glutathione, superoxide dismutase, and malondialdehyde, were assessed by ELISA. Compound 3a effectively prevented cognitive impairment induced by the AD model, and its effects were comparable to those of melatonin. In addition, this melatonin analogue with a donepezil fragment reduced AD-associated oxidative stress and suppressed model-associated increased A\u03b21-42 levels in the hippocampus. Our findings suggest that melatonin analogs containing donepezil fragments are promising therapeutic options for targeting oxidative stress associated with AD.<\/jats:p>","DOI":"10.3390\/ijms26146553","type":"journal-article","created":{"date-parts":[[2025,7,8]],"date-time":"2025-07-08T07:31:57Z","timestamp":1751959917000},"page":"6553","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Novel Melatonin Analog Containing Donepezil Fragment Prevents Cognitive Impairments and Associated Oxidative Stress in a Hybrid Rat Model of Melatonin Deficiency and icvA\u03b21-42"],"prefix":"10.3390","volume":"26","author":[{"given":"Petya","family":"Ivanova","sequence":"first","affiliation":[{"name":"Institute of Neurobiology, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lidia","family":"Kortenska","sequence":"additional","affiliation":[{"name":"Institute of Neurobiology, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6415-7336","authenticated-orcid":false,"given":"Violina T.","family":"Angelova","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Medical University of Sofia, 1000 Sofia, Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1640-5099","authenticated-orcid":false,"given":"Jana","family":"Tchekalarova","sequence":"additional","affiliation":[{"name":"Institute of Neurobiology, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"93","DOI":"10.36838\/v6i12.12","article-title":"Impacts of Alzheimer\u2019s Disease on Identity and Potential Therapeutic Approaches for Mitigating Identity Loss","volume":"6","author":"Mak","year":"2024","journal-title":"IJHSR"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3800","DOI":"10.1021\/acschemneuro.4c00339","article-title":"Alzheimer\u2019s Disease: Exploring the Landscape of Cognitive Decline","volume":"15","author":"Tenchov","year":"2024","journal-title":"ACS Chem. 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