Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine expansions in fly and mouse models of Huntington disease

@article{Ravikumar2004InhibitionOM,
  title={Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine expansions in fly and mouse models of Huntington disease},
  author={Brinda Ravikumar and Coralie Vacher and Zdenek Berger and Janet E. Davies and Shouqing Luo and Lourdes Garc{\'i}a Oroz and Francesco Scaravilli and Douglas F. Easton and Rainer Duden and Cahir J O'Kane and David C Rubinsztein},
  journal={Nature Genetics},
  year={2004},
  volume={36},
  pages={585-595}
}
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 autophagy, a key clearance pathway for mutant huntingtin fragments. This protects against… CONTINUE READING
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Polyglutamines placed into context

  • Y. Chai, L. Wu, J. D. Griffin, H. L. Paulson
  • Neuron
  • 2003

α - Synuclein is degraded by both autophagy and the proteasome

  • T. Schmelzle, M. N. TOR Hall
  • J . Biol . Chem .
  • 2003

Autophagosome formation in Mammalian cells

  • A. C. Gingras, B. Raught, N. Sonenberg
  • Cell Struct . Funct .
  • 2002

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