Huntingtin-Encoded Polyglutamine Expansions Form Amyloid-like Protein Aggregates In Vitro and In Vivo

@article{Scherzinger1997HuntingtinEncodedPE,
  title={Huntingtin-Encoded Polyglutamine Expansions Form Amyloid-like Protein Aggregates In Vitro and In Vivo},
  author={E. Scherzinger and R. Lurz and M. Turmaine and L. Mangiarini and B. Hollenbach and R. Hasenbank and G. Bates and S. W. Davies and H. Lehrach and E. Wanker},
  journal={Cell},
  year={1997},
  volume={90},
  pages={549-558}
}
The mechanism by which an elongated polyglutamine sequence causes neurodegeneration in Huntington's disease (HD) is unknown. In this study, we show that the proteolytic cleavage of a GST-huntingtin fusion protein leads to the formation of insoluble high molecular weight protein aggregates only when the polyglutamine expansion is in the pathogenic range. Electron micrographs of these aggregates revealed a fibrillar or ribbon-like morphology, reminiscent of scrapie prions and beta-amyloid fibrils… Expand
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References

SHOWING 1-10 OF 98 REFERENCES
Formation of Neuronal Intranuclear Inclusions Underlies the Neurological Dysfunction in Mice Transgenic for the HD Mutation
Cellular localization of the Huntington's disease protein and discrimination of the normal and mutated form
Polyglutamine expansion as a pathological epitope in Huntington's disease and four dominant cerebellar ataxias
Widespread expression of Huntington's disease gene (IT15) protein product
Characterization and localization of the Huntington disease gene product.
A huntingtin-associated protein enriched in brain with implications for pathology
Huntingtin and DRPLA proteins selectively interact with the enzyme GAPDH
Transgenic models of Huntington's disease.
  • K. Sathasivam, C. Hobbs, +5 authors G. Bates
  • Biology, Medicine
  • Philosophical transactions of the Royal Society of London. Series B, Biological sciences
  • 1999
...
1
2
3
4
5
...