Rapamycin alleviates toxicity of different aggregate-prone proteins - PubMed (original) (raw)

. 2006 Feb 1;15(3):433-42.

doi: 10.1093/hmg/ddi458. Epub 2005 Dec 20.

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Rapamycin alleviates toxicity of different aggregate-prone proteins

Zdenek Berger et al. Hum Mol Genet. 2006.

Abstract

Many neurodegenerative diseases are caused by intracellular, aggregate-prone proteins, including polyglutamine-expanded huntingtin in Huntington's disease (HD) and mutant tau in fronto-temporal dementia/tauopathy. Previously, we showed that rapamycin, an autophagy inducer, enhances mutant huntingtin fragment clearance and attenuated toxicity. Here we show much wider applications for this approach. Rapamycin enhances the autophagic clearance of different proteins with long polyglutamines and a polyalanine-expanded protein, and reduces their toxicity. Rapamycin also reduces toxicity in Drosophila expressing wild-type or mutant forms of tau and these effects can be accounted for by reductions in insoluble tau. Thus, our studies suggest that the scope for rapamycin as a potential therapeutic in aggregate diseases may be much broader than HD or even polyglutamine diseases.

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