Article
Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine expansions in fly and mouse models of Huntington disease.
Nature genetics - 1 Jun 2004
Ravikumar Brinda, Vacher Coralie, Berger Zdenek, Davies Janet E, Luo Shouqing, Oroz Lourdes G, Scaravilli Francesco, Easton Douglas F, Duden Rainer, O'Kane Cahir J, Rubinsztein David C
Abstract excerpt
Huntington disease is one of nine inherited neurodegenerative disorders caused by a polyglutamine tract expansion. Expanded polyglutamine proteins accumulate abnormally in intracellular aggregates. Here we show that mammalian target of rapamycin (mTOR) is sequestered in polyglutamine aggregates in cell models, transgenic mice and human brains. Sequestration of mTOR impairs its kinase activity and induces...
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