Rapamycin alleviates toxicity of different aggregate-prone proteins

Berger Z, Ravikumar B, Menzies FM, Oroz LG, Underwood BR, Pangalos MN, Schmitt I, Wullner U, Evert BO, O'Kane CJ, Rubinsztein DC · 2006 · Human Molecular Genetics · Atlas ID BER2006

What this study shows

Building on their earlier work with mutant huntingtin, the authors showed in cell models that rapamycin, used as an autophagy inducer, increased the clearance of several proteins with long polyglutamine tracts and of a polyalanine-expanded protein, and reduced their toxicity. In fruit flies expressing wild-type or mutant human tau, rapamycin reduced tau toxicity, and this went with less insoluble tau. The authors argued that inducing autophagy with rapamycin could be useful across several aggregate-prone protein diseases, not only Huntington's disease. Boundary: cultured cells and Drosophila overexpressing disease proteins; drawn from the abstract only; no mammalian in vivo or human data.

Abstract

ShowHide

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.

Read the full abstract on PubMed →

At a glance

Evidence type	M Molecular — cells, biochemistry, structure Marked M because it is molecular or in-vitro work (model: Mammalian cell lines (incl. COS cells) expressing polyglutamine- and polyalanine-expanded proteins; Drosophila expressing wild-type or mutant human tau) rather than a whole-organism health-outcome study. That is often exactly where causal biology gets established -- the code says which system the finding was shown in, and nothing about how good the work is.
Study type	5 - Mechanistic / In Vitro
Model system	Mammalian cell lines (incl. COS cells) expressing polyglutamine- and polyalanine-expanded proteins; Drosophila expressing wild-type or mutant human tau
Journal	Human Molecular Genetics
Year	2006
Peer reviewed	Yes
Record last updated	2026-10-01
Source	DOI 10.1093/hmg/ddi458 · PMID 16368705

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
Target	mTOR (autophagy induction)
Model	Mammalian cell lines; Drosophila
Effect	Rapamycin increased autophagic clearance and reduced toxicity of polyQ/polyA proteins and tau

In the Atlas

Cite this paper

ShowHide

Berger, Z., Ravikumar, B., Menzies, F. M., Oroz, L. G., Underwood, B. R., Pangalos, M. N., Schmitt, I., Wullner, U., Evert, B. O., O'Kane, C. J., & Rubinsztein, D. C. (2006). Rapamycin alleviates toxicity of different aggregate-prone proteins. Human Molecular Genetics. https://doi.org/10.1093/hmg/ddi458

@article{BER2006,
  author       = {Berger, Z. and Ravikumar, B. and Menzies, F. M. and Oroz, L. G. and Underwood, B. R. and Pangalos, M. N. and Schmitt, I. and Wullner, U. and Evert, B. O. and O'Kane, C. J. and Rubinsztein, D. C.},
  title        = {{Rapamycin alleviates toxicity of different aggregate-prone proteins}},
  journal      = {Human Molecular Genetics},
  year         = {2006},
  doi          = {10.1093/hmg/ddi458},
  note         = {PMID: 16368705},
}

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 BER2006) [Data set]. https://mtor-atlas.org/study/BER2006/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_BER2006,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record BER2006},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/BER2006/},
  doi          = {10.5281/zenodo.22059963}
}

Was this page useful?