Lamivudine, a reverse transcriptase inhibitor, rescues cognitive deficits in a mouse model of down syndrome

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• dc.contributor.author Martínez de Lagrán Cabredo, María
• dc.contributor.author Elizalde-Torrent, Aleix
• dc.contributor.author Paredes, Roger
• dc.contributor.author Clotet, Bonaventura
• dc.contributor.author Dierssen, Mara
• dc.date.accessioned 2022-11-02T07:28:55Z
• dc.date.available 2022-11-02T07:28:55Z
• dc.date.issued 2022
• dc.description.abstract An elevated activity of retrotransposons is increasingly recognized to be implicated in a wide range of neurodegenerative and neurodevelopmental diseases. Down syndrome (DS) is the most common genetic disorder associated with intellectual disability and a genetic form of Alzheimer's disease. For this reason, we hypothesized that treatment with reverse transcriptase inhibitors could ameliorate DS phenotypes. In this proof of concept study, we treated trisomic (Ts65Dn) mice, a model of DS, with lamivudine, a reverse transcriptase inhibitor. We detected a significant improvement of neurobehavioural phenotypes, and a complete rescue of the hippocampal-dependent recognition memory upon treatment with lamivudine. Despite clinical studies in patients with DS are warranted, this study lays the groundwork for a novel and actionable therapeutic approach.
• dc.description.sponsorship Agencia Estatal de Investigación. Grant Number: PID2019-110755RB-I00/AEI/10.13039/501100011033. Horizon 2020 Framework Programme. Grant Number: 848077
• dc.format.mimetype application/pdf
• dc.identifier.citation Martinez de Lagran M, Elizalde-Torrent A, Paredes R, Clotet B, Dierssen M. Lamivudine, a reverse transcriptase inhibitor, rescues cognitive deficits in a mouse model of down syndrome. J Cell Mol Med. 2022 Aug;26(15):4210-5. DOI: 10.1111/jcmm.17411
• dc.identifier.doi http://dx.doi.org/10.1111/jcmm.17411
• dc.identifier.issn 1582-1838
• dc.identifier.uri http://hdl.handle.net/10230/54648
• dc.language.iso eng
• dc.publisher Wiley
• dc.relation.ispartof J Cell Mol Med. 2022 Aug;26(15):4210-5
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PID2019-110755RB-I00
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/848077
• dc.rights © 2022 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword Down syndrome
• dc.subject.keyword Lamivudine
• dc.subject.keyword Memory
• dc.subject.keyword Retrotransposons
• dc.subject.keyword Reverse transcriptase inhibitor
• dc.title Lamivudine, a reverse transcriptase inhibitor, rescues cognitive deficits in a mouse model of down syndrome
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion