Modifiers of mutant huntingtin aggregation: Functional conservation of C. elegans-modifiers of polyglutamine aggregation

Eva Teuling, Annika Bourgonje, Sven Veenje, Karen Thijssen, Jelle de Boer, Joeri van der Velde, Morris Swertz, Ellen Nollen

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Protein aggregation is a common hallmark of a number of age-related neurodegenerative diseases, including Alzheimer's, Parkinson's, and polyglutamine-expansion disorders such as Huntington's disease, but how aggregation-prone proteins lead to pathology is not known. Using a genome-wide RNAi screen in a C. elegans-model for polyglutamine aggregation, we previously identified 186 genes that suppress aggregation. Using an RNAi screen for human orthologs of these genes, we here present 26 human genes that suppress aggregation of mutant huntingtin in a human cell line. Among these are genes that have not been previously linked to mutant huntingtin aggregation. They include those encoding eukaryotic translation initiation, elongation and translation factors, and genes that have been previously associated with other neurodegenerative diseases, like the ATP-ase family gene 3-like 2 (AFG3L2) and ubiquitin-like modifier activating enzyme 1 (UBA1). Unravelling the role of these genes will broaden our understanding of the pathogenesis of Huntington's disease.

Original languageEnglish
Number of pages20
JournalPLoS Currents
Issue numberRRN1255
Publication statusPublished - 2011

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