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Cited by 223Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchAmyotrophic Lateral Sclerosis Research

Chronic lithium administration to FTDP‐17 tau and GSK‐3β overexpressing mice prevents tau hyperphosphorylation and neurofibrillary tangle formation, but pre‐formed neurofibrillary tangles do not revert

Engel, Tobias, Goñi‐Oliver, Paloma, Lucas, José J., Avila, Jesús, Hernández, Félix·2006·Journal of Neurochemistry
DOI 10.1111/j.1471-4159.2006.04139.x
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Abstract

Glycogen synthase kinase-3 (GSK-3) has been proposed as the main kinase able to aberrantly phosphorylate tau in Alzheimer's disease (AD) and related tauopathies, raising the possibility of designing novel therapeutic interventions for AD based on GSK-3 inhibition. Lithium, a widely used drug for affective disorders, inhibits GSK-3 at therapeutically relevant concentrations. Therefore, it was of great interest to test the possible protective effects of lithium in an AD animal model based on GSK-3 overexpression. We had previously generated a double transgenic model, overexpressing GSK-3beta in a conditional manner, using the Tet-off system and tau protein carrying a triple FTDP-17 (frontotemporal dementia and parkinsonism linked to chromosome 17) mutation. This transgenic line shows tau hyperphosphorylation in hippocampal neurones accompanied by neurofibrillary tangles (NFTs). We used this transgenic model to address two issues: first, whether chronic lithium treatment is able to prevent the formation of aberrant tau aggregates that result from the overexpression of FTDP-17 tau and GSK-3beta; second, whether lithium is able to change back already formed NFTs in aged animals. Our data suggest that progression of the tauopathy can be prevented by administration of lithium when the first signs of neuropathology appear. Furthermore, it is still possible to partially reverse tau pathology in advanced stages of the disease, although NFT-like structures cannot be changed. The same re…

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  • GSK-3β inhibition reduces tau hyperphosphorylation and neurofibrillary tangle formation in tau-overexpressing transgenic mice.

    “Inhibition of GSK-3β may have dual benefits given that GSK-3β inhibition reduces tau hyperphosphorylation and NFT formation in tau-overexpressing transgenic mice (Noble et al., 2005; Engel et al., 2006; Leroy et al., 2010) and produces anticonvulsant effects against pentylenetetrazol-induced seizures in zebrafish larvae (Aourz et al., 2019).”

    From Tauopathy and Epilepsy Comorbidities and Underlying Mechanisms (2022) · cites this paper as Engel et al., 2006

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Authors
Engel, T., Goñi‐Oliver, P., Lucas, J. J., Avila, J., & Hernández, F.
Affiliations
Centro de Biología Molecular Severo Ochoa (ES)
ORCID
Venue
Journal of Neurochemistry
Publisher
Wiley
Published
2006-08-21
Volume
99
Issue
6
Pages
1445-1455
ISSN
  • 0022-3042 (ISSN-L)
  • 1471-4159
DOI
10.1111/j.1471-4159.2006.04139.x
OpenAlex
W2065961022
Cited by
223
References
1
Citations by year
2026: 4 · 2025: 14 · 2024: 11 · 2023: 5 · 2022: 6 · 2021: 12 · 2020: 16 · 2019: 8 · 2018: 7 · 2017: 8 · 2016: 9 · 2015: 12 · 2014: 8 · 2013: 11 · 2012: 11
FWCI
10.38
Type
journal article
Language
en
Open access
closed
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Journal of Neurochemistry (publishedVersion)
  • PubMed (publishedVersion)
  • DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
Funders
  • Fundación Ramón Areces
  • “la Caixa” Foundation
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
Keywords
lithium, glycogen synthase kinase-3β, tau hyperphosphorylation, neurofibrillary tangles, tauopathy, Alzheimer's disease, GSK3 inhibition, neuroprotection, transgenic mouse model
MeSH terms
Glycogen Synthase Kinase 3 beta, Age Factors, Animals, Atrophy, Doxycycline, Drug Administration Schedule, Hippocampus, Humans, Immunohistochemistry, Lithium, Mice, Transgenic, Microtubule-Associated Proteins, Neurons, Nuclear Proteins, Organic Chemicals, Phosphorylation, Blotting, Western, Microscopy, Immunoelectron, Neurofibrillary Tangles, tau Proteins, Glycogen Synthase Kinase 3, Mice, t-Complex Genome Region

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