DOI: 10.1523/jneurosci.23-17-06956.2003. Lack of Huntingtin-Associated Protein-1 Causes Neuronal Death Resembling Hypothalamic Degeneration in Huntington's Disease

Lack of Huntingtin-Associated Protein-1 Causes Neuronal Death Resembling Hypothalamic Degeneration in Huntington's Disease

10.1523/jneurosci.23-17-06956.2003

Crossref journal-article

Society for Neuroscience

The Journal of Neuroscience (393)

Abstract

Huntington's disease (HD) is caused by a polyglutamine expansion in the disease protein huntingtin. The polyglutamine expansion causes huntingtin to interact abnormally with a number of proteins. However, it is unclear whether, and how, huntingtin-associated proteins are involved in the neurodegeneration in HD. Here, we show that huntingtin-associated protein-1 (HAP1), which is involved in intracellular trafficking of epidermal growth factor receptor (EGFR), is highly expressed in the hypothalamus. Mice lacking HAP1 die after birth because of depressed feeding activity. Terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling staining and electron microscopic examination revealed the degeneration in hypothalamic regions that control feeding behavior. Hypothalamic degeneration was also observed in HD transgenic mice that have a significant loss of body weight. Inhibition of HAP1 expression decreases EGFR signaling and cell viability, whereas overexpression of HAP1 enhances this signaling activity and inhibits mutant huntingtin-mediated cytotoxicity. These results suggest that the effect of mutant huntingtin on HAP1 and EGFR signaling may contribute to the hypothalamic neurodegeneration and loss of body weight in HD.

Bibliography

Li, S.-H., Yu, Z.-X., Li, C.-L., Nguyen, H.-P., Zhou, Y.-X., Deng, C., & Li, X.-J. (2003). Lack of Huntingtin-Associated Protein-1 Causes Neuronal Death Resembling Hypothalamic Degeneration in Huntingtonâs Disease. The Journal of Neuroscience, 23(17), 6956â6964.

Authors 7

Shi-Hua Li (first)
Zhao-Xue Yu (additional)
Cui-Lin Li (additional)
Huu-Phuc Nguyen (additional)
Yong-Xing Zhou (additional)
Chuxia Deng (additional)
Xiao-Jiang Li (additional)

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Dates

Type	When
Created	7 years, 4 months ago (April 13, 2018, 6:30 p.m.)
Deposited	2 years, 6 months ago (Feb. 23, 2023, 11:06 a.m.)
Indexed	1 month, 1 week ago (July 23, 2025, 8:30 a.m.)
Issued	22 years, 1 month ago (July 30, 2003)
Published	22 years, 1 month ago (July 30, 2003)
Published Online	22 years, 1 month ago (July 30, 2003)
Published Print	22 years, 1 month ago (July 30, 2003)

Funders 0

None

BibTeX

@article{Li_2003, title={Lack of Huntingtin-Associated Protein-1 Causes Neuronal Death Resembling Hypothalamic Degeneration in Huntington’s Disease}, volume={23}, ISSN={1529-2401}, url={http://dx.doi.org/10.1523/jneurosci.23-17-06956.2003}, DOI={10.1523/jneurosci.23-17-06956.2003}, number={17}, journal={The Journal of Neuroscience}, publisher={Society for Neuroscience}, author={Li, Shi-Hua and Yu, Zhao-Xue and Li, Cui-Lin and Nguyen, Huu-Phuc and Zhou, Yong-Xing and Deng, Chuxia and Li, Xiao-Jiang}, year={2003}, month=jul, pages={6956–6964} }

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