Huntingtin and the molecular pathogenesis of Huntington's disease. Fourth in molecular medicine review series.
Journal: 2005/April - EMBO Reports
ISSN: 1469-221X
Abstract:
Huntington's disease (HD) is a late-onset neurodegenerative disorder that is caused by a CAG repeat expansion in the IT15 gene, which results in a long stretch of polyglutamine close to the amino-terminus of the HD protein huntingtin (htt). The normal function of htt, and the molecular mechanisms that contribute to the disease pathogenesis, are in the process of being elucidated. In this review, we outline the potential functions of htt as defined by the proteins with which it has been found to interact. We then focus on evidence that supports a role for transcriptional dysfunction and impaired protein folding and degradation as early events in disease pathogenesis.
Relations:
Content
Citations
(111)
References
(28)
Pathways
(1)
Diseases
(1)
Chemicals
(4)
Organisms
(1)
Processes
(3)
Affiliates
(2)
Similar articles
Articles by the same authors
Discussion board
EMBO Rep 5(10): 958-963

Huntingtin and the molecular pathogenesis of Huntington's disease

Neurogenetics Laboratory, Medical and Molecular Genetics, GKT School of Medicine, King's College London, 8th Floor Guy's Tower, Guy's Hospital, London SE1 9RT, UK
Tel: +44 20 7188 3717; Fax: +44 20 7188 2585; ku.ca.lck.sciteneg@seldnal.naitsirhc
Received 2004 Jun 7; Accepted 2004 Aug 9.

Summary

Fourth in Molecular Medicine Review Series

Keywords: Huntington's disease, huntingtin, polyglutamine, transcription, chaperones, proteasome
Summary

Huntington's disease (HD) is a late-onset neurodegenerative disorder that is caused by a CAG repeat expansion in the IT15 gene, which results in a long stretch of polyglutamine close to the amino-terminus of the HD protein huntingtin (htt). The normal function of htt, and the molecular mechanisms that contribute to the disease pathogenesis, are in the process of being elucidated. In this review, we outline the potential functions of htt as defined by the proteins with which it has been found to interact. We then focus on evidence that supports a role for transcriptional dysfunction and impaired protein folding and degradation as early events in disease pathogenesis.

Acknowledgments

We apologize to our colleagues whose work could not be cited, or was cited indirectly, due to space limitations. We thank members of the Neurogenetics Laboratory for advice and comments on the manuscript.

Acknowledgments
Collaboration tool especially designed for Life Science professionals.Drag-and-drop any entity to your messages.