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Rapamycin attenuates the progression of tau pathology in P301S tau transgenic mice

Ozcelik, S. and Fraser, G. and Castets, P. and Schaeffer, V. and Skachokova, Z. and Breu, K. and Clavaguera, F. and Sinnreich, M. and Kappos, L. and Goedert, M. and Tolnay, M. and Winkler, D. T.. (2013) Rapamycin attenuates the progression of tau pathology in P301S tau transgenic mice. PLoS ONE, Vol. 8, H. 5 , e62459.

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Official URL: http://edoc.unibas.ch/dok/A6338138

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Abstract

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.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Clinical Neuroimmunology (Derfuss/Lindberg)
03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Neuromuscular Research (Sinnreich)
UniBasel Contributors:Sinnreich, Michael and Kappos, Ludwig
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Public Library of Science
e-ISSN:1932-6203
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:31 Aug 2018 06:39
Deposited On:10 Apr 2015 09:12

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