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

Ravikumar B, Vacher C, Berger Z, Davies JE, Luo S, Oroz LG, Scaravilli F, Easton DF, Duden R, O'Kane CJ, Rubinsztein DC · 2004 · Nature Genetics · Atlas ID RAV2004

What this study shows

Induced autophagy cleared toxic clumped proteins and improved symptoms in fly (rapamycin) and mouse (the rapalog CCI-779) models of Huntington's disease.

Abstract

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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.

Read the full abstract on PubMed →

At a glance

Evidence type	A Animal model Marked A because it is an animal intervention or observation study measuring an organismal outcome (model: Drosophila and mouse models of Huntington's disease); the code names the system studied -- animal work can be rigorous and still not be human data.
Study type	4 - Animal Study
Model system	Drosophila and mouse models of Huntington's disease
Journal	Nature Genetics
Year	2004
Peer reviewed	Yes
Record last updated	2026-10-01
Source	DOI 10.1038/ng1362 · PMID 15146184

Extracted findings

These fields were extracted from the paper with AI assistance and have not been checked against the source. Read them as a pointer into the paper, not as curated claims; where they disagree with the curated summary above, the curated summary stands.

Intervention	Rapamycin (mTOR inhibition)
Target	mTOR / autophagy
Model	Drosophila and mouse Huntington's disease models
Effect	mTOR inhibition induces autophagy and reduces polyglutamine toxicity in Huntington's disease models

In the Atlas

Cite this paper

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Ravikumar, B., Vacher, C., Berger, Z., Davies, J. E., Luo, S., Oroz, L. G., Scaravilli, F., Easton, D. F., Duden, R., O'Kane, C. J., & Rubinsztein, D. C. (2004). Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine expansions in fly and mouse models of Huntington disease. Nature Genetics. https://doi.org/10.1038/ng1362

@article{RAV2004,
  author       = {Ravikumar, B. and Vacher, C. and Berger, Z. and Davies, J. E. and Luo, S. and Oroz, L. G. and Scaravilli, F. and Easton, D. F. and Duden, R. and O'Kane, C. J. and Rubinsztein, D. C.},
  title        = {{Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine expansions in fly and mouse models of Huntington disease}},
  journal      = {Nature Genetics},
  year         = {2004},
  doi          = {10.1038/ng1362},
  note         = {PMID: 15146184},
}

Cite this Atlas record

The record is the Atlas's own work — the evidence label, the extracted findings and the links. It is cited as part of the dataset, not as the paper.

Barton, O. (2026). Oliver's mTOR Atlas (record RAV2004) [Data set]. https://mtor-atlas.org/study/RAV2004/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_RAV2004,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record RAV2004},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/RAV2004/},
  doi          = {10.5281/zenodo.22059963}
}

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