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Publication : Rapamycin attenuates the progression of tau pathology in P301S tau transgenic mice.

First Author  Ozcelik S Year  2013
Journal  PLoS One Volume  8
Issue  5 Pages  e62459
PubMed ID  23667480 Mgi Jnum  J:200535
Mgi Id  MGI:5508829 Doi  10.1371/journal.pone.0062459
Citation  Ozcelik S, et al. (2013) Rapamycin attenuates the progression of tau pathology in P301S tau transgenic mice. PLoS One 8(5):e62459
abstractText  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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