Lamivudine (3TC), a Nucleoside Reverse Transcriptase Inhibitor, Prevents the Neuropathological Alterations Present in Mutant Tau Transgenic Mice

The dysregulation of transposable elements contributes to neurodegenerative disorders. Previous studies have reported an increase in retrotransposon transcription in Drosophila models as well as in human tauopathies. In this context, we tested the possible protective effects of a reverse transcripta...

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Detalles Bibliográficos
Autores: Vallés-Saiz, Laura, Ávila, Jésus, Hernández Pérez, Félix
Tipo de recurso: artículo
Fecha de publicación:2023
País:España
Institución:Universidad Autónoma de Madrid
Repositorio:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglés
OAI Identifier:oai:repositorio.uam.es:10486/711061
Acceso en línea:http://hdl.handle.net/10486/711061
https://dx.doi.org/10.3390/ijms241311144
Access Level:acceso abierto
Palabra clave:Alzheimer´s disease
lamivudine
tau
transposons
Biología y Biomedicina / Biología
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spelling Lamivudine (3TC), a Nucleoside Reverse Transcriptase Inhibitor, Prevents the Neuropathological Alterations Present in Mutant Tau Transgenic MiceVallés-Saiz, LauraÁvila, JésusHernández Pérez, FélixAlzheimer´s diseaselamivudinetautransposonsBiología y Biomedicina / BiologíaThe dysregulation of transposable elements contributes to neurodegenerative disorders. Previous studies have reported an increase in retrotransposon transcription in Drosophila models as well as in human tauopathies. In this context, we tested the possible protective effects of a reverse transcriptase inhibitor, namely lamivudine (also known as 3TC), in P301S mice, an animal model of Alzheimer’s disease based on FTDP-17-tau overexpression. Transgenic P301S mice administered lamivudine through drinking water showed a decrease in the following histopathological marks typical of tauopathies: tau phosphorylation; inflammation; neuronal death; and hippocampal atrophy. Lamivudine treatment attenuated motor deficits (Rotarod test) and improved short-term memory (Y-maze test). To evaluate the role of tau in retrotransposition, we cotransfected HeLa cells with a plasmid containing a complete LINE-1 sequence and a neomycin reporter cassette designed for retrotransposition assays, and a plasmid with the tau sequence. LINE-1 insertion increased considerably in the cotransfection compared to the transfection without tau. In addition, lamivudine inhibited the insertion of LINE-1. Our data suggest that the progression of the tauopathy can be attenuated by the administration of lamivudine upon the first symptoms of neuropathologyWork in the laboratory of FH is funded by grants from the Spanish Ministry of Economy and Competitiveness (Ministerio de Economía, Industria y Competitividad, Gobierno de España, PID2020-113204GB-I00) and from the Comunidad de Madrid through Structural Funds of the European Union [S2017/BMD-3700 (NEUROMETAB-CM)]. Work in the laboratory of JA is funded by grants from the Spanish Ministry of Economy and Competitiveness (PGC-2018-09177-B-100).MDPIFacultad de Ciencias20232023-07-01research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10486/711061https://dx.doi.org/10.3390/ijms241311144reponame:Biblos-e Archivo. Repositorio Institucional de la UAMinstname:Universidad Autónoma de MadridInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:repositorio.uam.es:10486/7110612026-06-23T12:46:27Z
dc.title.none.fl_str_mv Lamivudine (3TC), a Nucleoside Reverse Transcriptase Inhibitor, Prevents the Neuropathological Alterations Present in Mutant Tau Transgenic Mice
title Lamivudine (3TC), a Nucleoside Reverse Transcriptase Inhibitor, Prevents the Neuropathological Alterations Present in Mutant Tau Transgenic Mice
spellingShingle Lamivudine (3TC), a Nucleoside Reverse Transcriptase Inhibitor, Prevents the Neuropathological Alterations Present in Mutant Tau Transgenic Mice
Vallés-Saiz, Laura
Alzheimer´s disease
lamivudine
tau
transposons
Biología y Biomedicina / Biología
title_short Lamivudine (3TC), a Nucleoside Reverse Transcriptase Inhibitor, Prevents the Neuropathological Alterations Present in Mutant Tau Transgenic Mice
title_full Lamivudine (3TC), a Nucleoside Reverse Transcriptase Inhibitor, Prevents the Neuropathological Alterations Present in Mutant Tau Transgenic Mice
title_fullStr Lamivudine (3TC), a Nucleoside Reverse Transcriptase Inhibitor, Prevents the Neuropathological Alterations Present in Mutant Tau Transgenic Mice
title_full_unstemmed Lamivudine (3TC), a Nucleoside Reverse Transcriptase Inhibitor, Prevents the Neuropathological Alterations Present in Mutant Tau Transgenic Mice
title_sort Lamivudine (3TC), a Nucleoside Reverse Transcriptase Inhibitor, Prevents the Neuropathological Alterations Present in Mutant Tau Transgenic Mice
dc.creator.none.fl_str_mv Vallés-Saiz, Laura
Ávila, Jésus
Hernández Pérez, Félix
author Vallés-Saiz, Laura
author_facet Vallés-Saiz, Laura
Ávila, Jésus
Hernández Pérez, Félix
author_role author
author2 Ávila, Jésus
Hernández Pérez, Félix
author2_role author
author
dc.contributor.none.fl_str_mv Facultad de Ciencias
dc.subject.none.fl_str_mv Alzheimer´s disease
lamivudine
tau
transposons
Biología y Biomedicina / Biología
topic Alzheimer´s disease
lamivudine
tau
transposons
Biología y Biomedicina / Biología
description The dysregulation of transposable elements contributes to neurodegenerative disorders. Previous studies have reported an increase in retrotransposon transcription in Drosophila models as well as in human tauopathies. In this context, we tested the possible protective effects of a reverse transcriptase inhibitor, namely lamivudine (also known as 3TC), in P301S mice, an animal model of Alzheimer’s disease based on FTDP-17-tau overexpression. Transgenic P301S mice administered lamivudine through drinking water showed a decrease in the following histopathological marks typical of tauopathies: tau phosphorylation; inflammation; neuronal death; and hippocampal atrophy. Lamivudine treatment attenuated motor deficits (Rotarod test) and improved short-term memory (Y-maze test). To evaluate the role of tau in retrotransposition, we cotransfected HeLa cells with a plasmid containing a complete LINE-1 sequence and a neomycin reporter cassette designed for retrotransposition assays, and a plasmid with the tau sequence. LINE-1 insertion increased considerably in the cotransfection compared to the transfection without tau. In addition, lamivudine inhibited the insertion of LINE-1. Our data suggest that the progression of the tauopathy can be attenuated by the administration of lamivudine upon the first symptoms of neuropathology
publishDate 2023
dc.date.none.fl_str_mv 2023
2023-07-01
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10486/711061
https://dx.doi.org/10.3390/ijms241311144
url http://hdl.handle.net/10486/711061
https://dx.doi.org/10.3390/ijms241311144
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:Biblos-e Archivo. Repositorio Institucional de la UAM
instname:Universidad Autónoma de Madrid
instname_str Universidad Autónoma de Madrid
reponame_str Biblos-e Archivo. Repositorio Institucional de la UAM
collection Biblos-e Archivo. Repositorio Institucional de la UAM
repository.name.fl_str_mv
repository.mail.fl_str_mv
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