{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:57:47Z","timestamp":1792789067951,"version":"4.5.0"},"reference-count":68,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T00:00:00Z","timestamp":1789776000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Russian Science Foundation","award":["22-15-00141-P"],"award-info":[{"award-number":["22-15-00141-P"]}],"id":[{"id":"https:\/\/ror.org\/03y2gwe85","id-type":"ROR","asserted-by":"crossref"}]},{"award":["22-15-00141-P"],"award-info":[{"award-number":["22-15-00141-P"]}],"id":[{"id":"https:\/\/ror.org\/03y2gwe85","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Cell-based gene therapy is a promising strategy to promote regeneration in Alzheimer\u2019s disease (AD). Neurotrophin-3 (NT-3) plays a key role in neuroprotection and brain regeneration, providing a strong rationale for its exogenous delivery. Olfactory ensheathing cells (OECs) have high regenerative potential and serve as a vehicle for local gene delivery. We investigated the therapeutic potential of NT-3-expressing OECs in an A\u03b21\u201342-induced AD model in female Wistar rats. Rat OECs were transduced with an Ad5RGD-CAG-NT-3 adenoviral vector, and NT-3 levels were measured in vitro using ELISA. To evaluate the efficacy of NT-3-transduced and non-transduced OECs, we performed behavioral assessments and measured the concentration of NT-3, A\u03b21\u201342, and pTau levels in brain specimens 4 weeks post-transplantation. Transduced OECs exhibited markedly increased NT-3 secretion in vitro compared with non-transduced cells. All OEC-treated groups showed improved cognitive performance following transplantation. However, only NT-3-transduced OECs significantly increased brain NT-3 and reduced A\u03b21\u201342 levels, indicating an enhanced therapeutic effect mediated by NT-3 overexpression. None of the cell grafts affected pTau levels. These findings demonstrate that OEC transplantation improves functional outcomes in experimental AD, while NT-3 overexpression provides biochemical benefits by reducing amyloid accumulation. Taken together, our findings support further investigation of NT-3-expressing OECs as a cell-based gene therapy for AD.<\/jats:p>","DOI":"10.3390\/cells15181706","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T09:01:38Z","timestamp":1789981298000},"page":"1706","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["NT-3-Expressing Olfactory Ensheathing Cells Reduce Brain A\u03b21\u201342 Accumulation and Improve Cognitive Performance in a Rat Model of Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8385-3559","authenticated-orcid":false,"given":"Ekaterina Konstantinovna","family":"Karsuntseva","sequence":"first","affiliation":[{"name":"Department of Fundamental and Applied Neurobiology, V.P. Serbsky Federal Medical Research Center for Psychiatry and Narcology, Moscow 119034, Russia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0654-7483","authenticated-orcid":false,"given":"Anastasia Denisovna","family":"Voronova","sequence":"additional","affiliation":[{"name":"Department of Fundamental and Applied Neurobiology, V.P. Serbsky Federal Medical Research Center for Psychiatry and Narcology, Moscow 119034, Russia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"given":"Olga Vladislavovna","family":"Stepanova","sequence":"additional","affiliation":[{"name":"Department of Fundamental and Applied Neurobiology, V.P. Serbsky Federal Medical Research Center for Psychiatry and Narcology, Moscow 119034, Russia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"}]},{"given":"Aleksei Anatolyevich","family":"Stepanenko","sequence":"additional","affiliation":[{"name":"Department of Fundamental and Applied Neurobiology, V.P. Serbsky Federal Medical Research Center for Psychiatry and Narcology, Moscow 119034, Russia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8505-5769","authenticated-orcid":false,"given":"Valentina Sergeevna","family":"Shishkina","sequence":"additional","affiliation":[{"name":"Department of Fundamental and Applied Neurobiology, V.P. Serbsky Federal Medical Research Center for Psychiatry and Narcology, Moscow 119034, Russia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6915-2078","authenticated-orcid":false,"given":"Grigorii Andreevich","family":"Fursa","sequence":"additional","affiliation":[{"name":"Department of Fundamental and Applied Neurobiology, V.P. Serbsky Federal Medical Research Center for Psychiatry and Narcology, Moscow 119034, Russia"},{"name":"Department of Medical Nanobiotechnology, Pirogov Russian National Research Medical University, Moscow 117513, Russia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"validation","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9377-6673","authenticated-orcid":false,"given":"Andrey Victorovich","family":"Chadin","sequence":"additional","affiliation":[{"name":"Department of Fundamental and Applied Neurobiology, V.P. Serbsky Federal Medical Research Center for Psychiatry and Narcology, Moscow 119034, Russia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"}]},{"given":"Igor Vladimirovich","family":"Reshetov","sequence":"additional","affiliation":[{"name":"University Clinical Hospital No. 1, Sechenov First Moscow State Medical University (Sechenov University), Moscow 119435, Russia"},{"name":"Academy of Postgraduate Education, Federal Research and Clinical Center, Federal Medical-Biological Agency, Moscow 125371, Russia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"resources","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6942-5531","authenticated-orcid":false,"given":"Olga Ivanovna","family":"Gurina","sequence":"additional","affiliation":[{"name":"Department of Fundamental and Applied Neurobiology, V.P. Serbsky Federal Medical Research Center for Psychiatry and Narcology, Moscow 119034, Russia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"data-curation","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4386-7897","authenticated-orcid":false,"given":"Vladimir Pavlovich","family":"Chekhonin","sequence":"additional","affiliation":[{"name":"Department of Fundamental and Applied Neurobiology, V.P. Serbsky Federal Medical Research Center for Psychiatry and Narcology, Moscow 119034, Russia"},{"name":"Department of Medical Nanobiotechnology, Pirogov Russian National Research Medical University, Moscow 117513, Russia"},{"name":"Research Institute of Personalized Medicine, Endocrinology Research Centre, Moscow 117292, Russia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Alzheimer\u2019s Association (2024). 2024 Alzheimer\u2019s disease facts and figures. 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