Huntingtin–protein interactions and the pathogenesis of Huntington's disease

• Published in: Trends in genetics 2004-03, Vol.20 (3), p.146-154
• Main Authors: Li, Shi-Hua, Li, Xiao-Jiang
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Fundamental and applied biological sciences. Psychology; Genetics of eukaryotes. Biological and molecular evolution; Humans; Huntingtin Protein; Huntington Disease - etiology; Huntington Disease - metabolism; Huntington Disease - pathology; Medical sciences; Molecular and cellular biology; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Neurology; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Peptides; Protein Binding; Transcription Factors - genetics; Transcription Factors - metabolism; Trinucleotide Repeats
• ISSN: 0168-9525
• DOI: 10.1016/j.tig.2004.01.008

At least nine inherited neurodegenerative diseases share a polyglutamine expansion in their respective disease proteins. These diseases show distinct neuropathological changes, suggesting that protein environment and protein–protein interactions play an important role in the specific neuropathology. A gain of toxic function as a result of an expanded polyglutamine tract can cause the protein huntingtin to interact abnormally with a variety of proteins, resulting in the complex of neuropathological changes seen in Huntington's disease. Recent studies have identified several huntingtin-interacting proteins that might be associated with the normal function of huntingtin and/or involved in the pathology of Huntington's disease. In this article, we focus on the potential roles of huntingtin–protein interactions in the pathogenesis of Huntington's disease.