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Rapamycin Attenuates the Progression of Tau Pathology in P301S Tau Transgenic Mice

Altered autophagy contributes to the pathogenesis of Alzheimer’s disease and other tauopathies, for which curative treatment options are still lacking. We have recently shown that trehalose reduces tau pathology in a tauopathy mouse model by stimulation of autophagy. Here, we studied the effect of t...

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Autores principales: Ozcelik, Sefika, Fraser, Graham, Castets, Perrine, Schaeffer, Véronique, Skachokova, Zhiva, Breu, Karin, Clavaguera, Florence, Sinnreich, Michael, Kappos, Ludwig, Goedert, Michel, Tolnay, Markus, Winkler, David Theo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3646815/
https://www.ncbi.nlm.nih.gov/pubmed/23667480
http://dx.doi.org/10.1371/journal.pone.0062459
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author Ozcelik, Sefika
Fraser, Graham
Castets, Perrine
Schaeffer, Véronique
Skachokova, Zhiva
Breu, Karin
Clavaguera, Florence
Sinnreich, Michael
Kappos, Ludwig
Goedert, Michel
Tolnay, Markus
Winkler, David Theo
author_facet Ozcelik, Sefika
Fraser, Graham
Castets, Perrine
Schaeffer, Véronique
Skachokova, Zhiva
Breu, Karin
Clavaguera, Florence
Sinnreich, Michael
Kappos, Ludwig
Goedert, Michel
Tolnay, Markus
Winkler, David Theo
author_sort Ozcelik, Sefika
collection PubMed
description Altered autophagy contributes to the pathogenesis of Alzheimer’s disease and other tauopathies, for which curative treatment options are still lacking. We have recently shown that trehalose reduces tau pathology in a tauopathy mouse model by stimulation of autophagy. Here, we studied the effect of the autophagy inducing drug rapamycin on the progression of tau pathology in P301S mutant tau transgenic mice. Rapamycin treatment resulted in a significant reduction in cortical tau tangles, less tau hyperphosphorylation, and lowered levels of insoluble tau in the forebrain. The favourable effect of rapamycin on tau pathology was paralleled by a qualitative reduction in astrogliosis. These effects were visible with early preventive or late treatment. We further noted an accumulation of the autophagy associated proteins p62 and LC3 in aged tangle bearing P301S mice that was lowered upon rapamycin treatment. Thus, rapamycin treatment defers the progression of tau pathology in a tauopathy animal model and autophagy stimulation may constitute a therapeutic approach for patients suffering from tauopathies.
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spelling pubmed-36468152013-05-10 Rapamycin Attenuates the Progression of Tau Pathology in P301S Tau Transgenic Mice Ozcelik, Sefika Fraser, Graham Castets, Perrine Schaeffer, Véronique Skachokova, Zhiva Breu, Karin Clavaguera, Florence Sinnreich, Michael Kappos, Ludwig Goedert, Michel Tolnay, Markus Winkler, David Theo PLoS One Research Article Altered autophagy contributes to the pathogenesis of Alzheimer’s disease and other tauopathies, for which curative treatment options are still lacking. We have recently shown that trehalose reduces tau pathology in a tauopathy mouse model by stimulation of autophagy. Here, we studied the effect of the autophagy inducing drug rapamycin on the progression of tau pathology in P301S mutant tau transgenic mice. Rapamycin treatment resulted in a significant reduction in cortical tau tangles, less tau hyperphosphorylation, and lowered levels of insoluble tau in the forebrain. The favourable effect of rapamycin on tau pathology was paralleled by a qualitative reduction in astrogliosis. These effects were visible with early preventive or late treatment. We further noted an accumulation of the autophagy associated proteins p62 and LC3 in aged tangle bearing P301S mice that was lowered upon rapamycin treatment. Thus, rapamycin treatment defers the progression of tau pathology in a tauopathy animal model and autophagy stimulation may constitute a therapeutic approach for patients suffering from tauopathies. Public Library of Science 2013-05-07 /pmc/articles/PMC3646815/ /pubmed/23667480 http://dx.doi.org/10.1371/journal.pone.0062459 Text en © 2013 Ozcelik et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Ozcelik, Sefika
Fraser, Graham
Castets, Perrine
Schaeffer, Véronique
Skachokova, Zhiva
Breu, Karin
Clavaguera, Florence
Sinnreich, Michael
Kappos, Ludwig
Goedert, Michel
Tolnay, Markus
Winkler, David Theo
Rapamycin Attenuates the Progression of Tau Pathology in P301S Tau Transgenic Mice
title Rapamycin Attenuates the Progression of Tau Pathology in P301S Tau Transgenic Mice
title_full Rapamycin Attenuates the Progression of Tau Pathology in P301S Tau Transgenic Mice
title_fullStr Rapamycin Attenuates the Progression of Tau Pathology in P301S Tau Transgenic Mice
title_full_unstemmed Rapamycin Attenuates the Progression of Tau Pathology in P301S Tau Transgenic Mice
title_short Rapamycin Attenuates the Progression of Tau Pathology in P301S Tau Transgenic Mice
title_sort rapamycin attenuates the progression of tau pathology in p301s tau transgenic mice
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3646815/
https://www.ncbi.nlm.nih.gov/pubmed/23667480
http://dx.doi.org/10.1371/journal.pone.0062459
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