Volume 7 Supplement 1

Proceedings of the 2011 International Conference on Molecular Neurodegeneration

Open Access

Novel circuitry and molecular pathogenic mechanisms in Huntington's disease

  • X William Yang1
Molecular Neurodegeneration20127(Suppl 1):L18

DOI: 10.1186/1750-1326-7-S1-L18

Published: 7 February 2012

Background

Huntington's disease (HD) is one of the most common inherited neurodegenerative disorders and is characterized clinically by the mid-age onset of progressive motor, cognitive and psychiatric deficits.

Methods

HD is caused by a CAG repeat expansion encoding an expanded glutamine repeat near the N-terminus of the huntingtin protein. How mutant huntingtin (mhtt) causes progressive and selective degeneration of striatal and cortical neurons, leading to symptoms of HD, remains unclear. In this presentation, I will describe a novel reductionist approach to use Cre/LoxP conditional Bacterial Artificial Chromosome (BAC) transgenic mouse models expressing full-length mhtt to dissect circuitry and molecular pathogenic mechanisms in HD.

Results

Our study defines the distinct but synergistic roles of cortical and striatal projection neurons in HD pathogenesis, and uncovers novel evidence for HD being a non-cell-autonomous disease. Finally, we show that phosphorylation of a small mhtt N-terminus domain can act as a molecular switch to suppress HD pathogenesis in vivo.

Conclusion

Together, our studies provide novel mechanistic and therapeutic insights for HD.

Authors’ Affiliations

(1)
Center for Neurobehavioral Genetics, Semel Institute, Department of Psychiatry & Biobehavioral Studies, David Geffen School of Medicine at UCLA

Copyright

© Yang; licensee BioMed Central Ltd. 2012

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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