title: Modifiers of mutant huntingtin aggregation: functional conservation of C. elegans-modifiers of polyglutamine aggregation.
abstract: 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.
authors.affiliation: Department of Genetics, University Medical Centre Groningen, University of Groningen, PO Box 30001, 9700 RB Groningen; Groningen Bioinformatics Centre, Nijenborgh 7, 9747 AG Groningen, The Netherlands and Genomics Coordination Center, Department of Genetics, University Medical Center Groningen and Groningen Bioinformatics Center, University of Groningen, P.O. Box 30001, 9700 RB, Groningen, The Netherlands.
authors.forename: Eva
authors.initials: E
authors.lastname: Teuling
authors.forename: Annika
authors.initials: A
authors.lastname: Bourgonje
authors.forename: Sven
authors.initials: S
authors.lastname: Veenje
authors.forename: Karen
authors.initials: K
authors.lastname: Thijssen
authors.forename: Jelle
authors.initials: J
authors.lastname: de Boer
authors.forename: Joeri
authors.initials: J
authors.lastname: van der Velde
authors.forename: Morris
authors.initials: M
authors.lastname: Swertz
authors.forename: Ellen
authors.initials: E
authors.lastname: Nollen