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Author Notes:

Correspondence: Xiao-Jiang Li: xli2@emory.edu

Authors' contributions: The experimental work was designed and performed by CEW.

SHL was involved in experiment design and manuscript writing.

XJL was involved in experiment design and manuscript writing.

All authors read and approved the final manuscript.

Disclosures: The authors declare that they have no competing interests.

Subjects:

Research Funding:

This work is supported by grants from the National Institutes of Health (AG019206 and NS041669 to XJL; NS045016 and AG031153 to SHL).

Lack of interleukin-1 type 1 receptor enhances the accumulation of mutant huntingtin in the striatum and exacerbates the neurological phenotypes of Huntington's disease mice

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Journal Title:

Molecular Brain

Volume:

Volume 3, Number 33

Publisher:

, Pages 1-7

Type of Work:

Article | Final Publisher PDF

Abstract:

Huntington's disease results from expansion of a glutamine repeat (>36 glutamines) in the N-terminal region of huntingtin (htt) and is characterized by preferential neurodegeneration in the striatum of the brain. N171-82Q mice that express N-terminal 171 amino acids of htt with an 82-glutamine repeat show severe neurological phenotypes and die early, suggesting that N-terminal mutant htt is pathogenic. In addition, various cellular factors and genetic modifiers are found to modulate the cytotoxicity of mutant htt. Understanding the contribution of these factors to HD pathogenesis will help identify therapeutics for this disease. To investigate the role of interleukin type 1 (IL-1), a cytokine that has been implicated in various neurological diseases, in HD neurological symptoms, we crossed N171-82Q mice to type I IL-1 receptor (IL-1RI) knockout mice. Mice lacking IL-1RI and expressing N171-82Q show more severe neurological symptoms than N171-82Q or IL-1RI knockout mice, suggesting that lack of IL-1RI can promote the neuronal toxicity of mutant htt. Lack of IL-1RI also increases the accumulation of transgenic mutant htt in the striatum in N171-82Q mice. Since IL-1RI signaling mediates both toxic and protective effects on neurons, its basal function and protective effects may be important for preventing the neuropathology seen in HD.

Copyright information:

© 2010 Wang et al

This is an Open Access work distributed under the terms of the Creative Commons Attribution 2.0 Generic License (http://creativecommons.org/licenses/by/2.0/).

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