Scientific article
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English

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

Published inPloS one, vol. 8, no. 5, e62459
Publication date2013
First online date2013-05-07
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.

Keywords
  • Animals
  • Astrocytes / drug effects
  • Astrocytes / pathology
  • Disease Progression
  • Humans
  • Mice
  • Mice, Transgenic
  • Phosphorylation / drug effects
  • Sirolimus / pharmacology
  • Sirolimus / therapeutic use
  • Solubility
  • Tauopathies / drug therapy
  • Tauopathies / genetics
  • Tauopathies / metabolism
  • Tauopathies / pathology
  • Time Factors
  • Tau Proteins / chemistry
  • Tau Proteins / genetics
  • Tau Proteins / metabolism
Affiliation entities Not a UNIGE publication
Citation (ISO format)
OZCELIK, Sefika et al. Rapamycin Attenuates the Progression of Tau Pathology in P301S Tau Transgenic Mice. In: PloS one, 2013, vol. 8, n° 5, p. e62459. doi: 10.1371/journal.pone.0062459
Main files (1)
Article (Published version)
Identifiers
Journal ISSN1932-6203
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16downloads

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