Lamivudine (3TC), a Nucleoside Reverse Transcriptase Inhibitor, Prevents the Neuropathological Alterations Present in Mutant Tau Transgenic Mice
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Abstract
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.
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Recent studies in two mouse models of tauopathy and in AD model organoids indicate that 3TC suppresses toxicity.
“Recent studies in two mouse models of tauopathy (Vallés-Saiz et al. 2023, Wahl et al. 2023) and in AD model organoids (Sun et al. 2023) also indicate that 3TC suppresses toxicity.”
From The Role of Retrotransposons and Endogenous Retroviruses in Age-Dependent Neurodegenerative Disorders (2024) · cites this paper as Vallés-Saiz et al. 2023
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- Authors
- Vallés-Saiz, L., Ávila, J., & Hernández, F.
- Affiliations
- Centro de Biología Molecular “Severo Ochoa”, CSIC/UAM, Universidad Autónoma de Madrid, Cantoblanco, 28049 Madrid, Spain
- Consejo Superior de Investigaciones Científicas (ES)
- Corresponding author
- Hernández, Félix
- Venue
- International Journal of Molecular Sciences
- Publisher
- MDPI AG
- Published
- 2023-07-06
- Volume
- 24
- Issue
- 13
- Pages
- 11144
- ISSN
- 1422-0067 (ISSN-L)
- PMC
- PMC10342792
- OpenAlex
- W4383551588
- Cited by
- 35
- References
- 50
- Citations by year
- 2026: 7 · 2025: 16 · 2024: 11
- FWCI
- 6.04
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- International Journal of Molecular Sciences (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion, cc-by)
- Hispana (submittedVersion)
- Biblos-e Archivo (Universidad Autónoma de Madrid) (submittedVersion, cc-by)
- Funders
- Spanish Ministry of Economy and Competitiveness (PID2020-113204GB-I00, S2017/BMD-3700, PGC-2018-09177-B-100)
- Comunidad de Madrid through Structural Funds of the European Union (PID2020-113204GB-I00, S2017/BMD-3700, PGC-2018-09177-B-100)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- lamivudine, nucleoside reverse transcriptase inhibitors, tauopathy, FTDP-17, Alzheimer's disease, tau phosphorylation, neuroinflammation, neuronal cell death, hippocampal atrophy, motor impairment, short-term memory, LINE-1 retrotransposition
- MeSH terms
- Animals, Disease Models, Animal, HeLa Cells, Humans, Mice, Transgenic, tau Proteins, Reverse Transcriptase Inhibitors, Lamivudine, Tauopathies, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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