Skip Navigation



Human Molecular Genetics Advance Access published online on October 4, 2005
Human Molecular Genetics, doi:10.1093/hmg/ddi372
This Article
Right arrow FREE Full Text (PDF) Freely available
Right arrow Supplementary Material
Right arrow All Versions of this Article:
14/22/3425    most recent
ddi372v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Vacher, C.
Right arrow Articles by Rubinsztein, D. C
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Vacher, C.
Right arrow Articles by Rubinsztein, D. C
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2005. Published by Oxford University Press. All rights reserved
Received July 22, 2005
Revised September 28, 2005
Accepted September 28, 2005

Article

Overexpression of yeast hsp104 reduces polyglutamine aggregation and prolongs survival of a transgenic mouse model of Huntington's disease

Coralie Vacher 1, Lourdes Garcia-Oroz 1, and David C Rubinsztein 1*

1 Department of Medical Genetics, Cambridge Institute for Medical Research, Wellcome/MRC Building, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 2XY, UK

* To whom correspondence should be addressed.
David C Rubinsztein, E-mail: dcr1000{at}hermes.cam.ac.uk


  Abstract

Huntington's disease is a devastating neurodegenerative condition associated with the formation of intraneuronal aggregates by mutant huntingtin. Aggregate formation is a property shared by the nine related diseases caused by polyglutamine codon expansion mutations, and also by other neurodegenerative conditions like Parkinsons's disease. The roles of aggregates and aggregation in these diseases has been a subject of heated controversy. Here we have addressed the question in vivo by generating a new transgenic mouse overexpressing the yeast chaperone hsp104, since hsp104 overexpression reduced mutant huntingtin aggregation and toxicity in cell models. Hsp104 has no close mammalian orthologues and does not appear to have effects on mammalian cell death pathways. We crossed hsp104 transgenic mice with mice expressing the first 171 residues of mutant huntingtin. Hsp104 reduced aggregate formation and prolonged the lifespan of the HD mice by 20%. This protection may be mediated at the level of changing the conformation of a putative toxic monomer, reducing oligomerisation or aggregation, reducing the levels of oligomeric species or aggregates, or combinations of these non-mutually exclusive possibilities.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Genes Dev.Home page
M. L. Duennwald and S. Lindquist
Impaired ERAD and ER stress are early and specific events in polyglutamine toxicity
Genes & Dev., December 1, 2008; 22(23): 3308 - 3319.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
A. L. Orr, S. Huang, M. A. Roberts, J. C. Reed, S. Li, and X.-J. Li
Sex-dependent Effect of BAG1 in Ameliorating Motor Deficits of Huntington Disease Transgenic Mice
J. Biol. Chem., June 6, 2008; 283(23): 16027 - 16036.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
S. Luo, H. Mizuta, and D. C. Rubinsztein
p21-activated kinase 1 promotes soluble mutant huntingtin self-interaction and enhances toxicity
Hum. Mol. Genet., March 15, 2008; 17(6): 895 - 905.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
J.-C. Lievens, M. Iche, M. Laval, C. Faivre-Sarrailh, and S. Birman
AKT-sensitive or insensitive pathways of toxicity in glial cells and neurons in Drosophila models of Huntington's disease
Hum. Mol. Genet., March 15, 2008; 17(6): 882 - 894.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
E. Teuling, S. Ahmed, E. Haasdijk, J. Demmers, M. O. Steinmetz, A. Akhmanova, D. Jaarsma, and C. C. Hoogenraad
Motor Neuron Disease-Associated Mutant Vesicle-Associated Membrane Protein-Associated Protein (VAP) B Recruits Wild-Type VAPs into Endoplasmic Reticulum-Derived Tubular Aggregates
J. Neurosci., September 5, 2007; 27(36): 9801 - 9815.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
A. Zourlidou, T. Gidalevitz, M. Kristiansen, C. Landles, B. Woodman, D. J. Wells, D. S. Latchman, J. de Belleroche, S. J. Tabrizi, R. I. Morimoto, et al.
Hsp27 overexpression in the R6/2 mouse model of Huntington's disease: chronic neurodegeneration does not induce Hsp27 activation
Hum. Mol. Genet., May 1, 2007; 16(9): 1078 - 1090.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
M. L. Duennwald, S. Jagadish, P. J. Muchowski, and S. Lindquist
Flanking sequences profoundly alter polyglutamine toxicity in yeast
PNAS, July 18, 2006; 103(29): 11045 - 11050.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
Z. Berger, J. E. Davies, S. Luo, M. Y. Pasco, I. Majoul, C. J. O'Kane, and D. C. Rubinsztein
Deleterious and protective properties of an aggregate-prone protein with a polyalanine expansion
Hum. Mol. Genet., February 1, 2006; 15(3): 453 - 465.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.