Skip Navigation

Human Molecular Genetics 2007 16(R2):R115-R123; doi:10.1093/hmg/ddm213
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
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 Shao, J.
Right arrow Articles by Diamond, M. I.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Shao, J.
Right arrow Articles by Diamond, M. I.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2007. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Polyglutamine diseases: emerging concepts in pathogenesis and therapy

Jieya Shao1,2 and Marc I. Diamond1,2,*

1 Department of Neurology and 2 Department of Cellular and Molecular Pharmacology, UCSF, San Francisco, CA 94143, USA

* To whom correspondence should be addressed at: GH-S572B, 600 16th Street, San Francisco, CA 94143, USA. Tel: +1 4155143646; Fax: +1 4155144112; Email: marc.diamond{at}ucsf.edu

Received June 22, 2007; Revised June 22, 2007; Accepted July 27, 2007

Polyglutamine diseases are a family of neurodegenerative conditions that each derive from a CAG triplet repeat expansion in a specific gene. This produces a pathogenic protein that contains a critically expanded tract of glutamines. These prototypical protein misfolding disorders include Huntington disease, spinobulbar muscular atrophy, dentatorubral-pallidoluysian atrophy and several spinocerebellar ataxias. This article reviews the emerging concepts in pathogenesis and therapy. Key ideas include the role of proteolytic cleavage, the importance of conformational change in the pathogenic proteins, the role of protein aggregation and the importance of transcriptional and metabolic disturbances. The relative role of functional perturbation in a target protein induced by a polyglutamine expansion is also discussed. Therapeutic strategies include counteracting cellular perturbations and direct targeting of polyglutamine protein expression, cleavage or conformation.


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
 Hum Mol GenetHome page
A. Chai, J. Withers, Y. H. Koh, K. Parry, H. Bao, B. Zhang, V. Budnik, and G. Pennetta
hVAPB, the causative gene of a heterogeneous group of motor neuron diseases in humans, is functionally interchangeable with its Drosophila homologue DVAP-33A at the neuromuscular junction
Hum. Mol. Genet., January 15, 2008; 17(2): 266 - 280.
[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.