title: Large-scale screen for modifiers of ataxin-3-derived polyglutamine-induced toxicity in Drosophila.
abstract: Polyglutamine (polyQ) diseases represent a neuropathologically heterogeneous group of disorders. The common theme of these disorders is an elongated polyQ tract in otherwise unrelated proteins. So far, only symptomatic treatment can be applied to patients suffering from polyQ diseases. Despite extensive research, the molecular mechanisms underlying polyQ-induced toxicity are largely unknown. To gain insight into polyQ pathology, we performed a large-scale RNAi screen in Drosophila to identify modifiers of toxicity induced by expression of truncated Ataxin-3 containing a disease-causing polyQ expansion. We identified various unknown modifiers of polyQ toxicity. Large-scale analysis indicated a dissociation of polyQ aggregation and toxicity.
authors.affiliation: Department of Neurology, University Medical Center, RWTH Aachen, Aachen, Germany.
authors.forename: Hannes
authors.initials: H
authors.lastname: VoSSfeldt
authors.forename: Malte
authors.initials: M
authors.lastname: Butzlaff
authors.forename: Katja
authors.initials: K
authors.lastname: PrüSSing
authors.forename: Róisín-Ana
authors.initials: RA
authors.lastname: Ní Chárthaigh
authors.forename: Peter
authors.initials: P
authors.lastname: Karsten
authors.forename: Anne
authors.initials: A
authors.lastname: Lankes
authors.forename: Sabine
authors.initials: S
authors.lastname: Hamm
authors.forename: Mikael
authors.initials: M
authors.lastname: Simons
authors.forename: Boris
authors.initials: B
authors.lastname: Adryan
authors.forename: Jörg B
authors.initials: JB
authors.lastname: Schulz
authors.forename: Aaron
authors.initials: A
authors.lastname: Voigt
mesh_terms: D000818:Animals; D000067699:Ataxin-3; D019295:Computational Biology; D029721:Drosophila Proteins / Q000737:chemistry / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000187:drug effects* / Q000378:metabolism*; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism*; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry / Q000633:toxicity*; D020836:Protein Structure, Quaternary; D034622:RNA Interference; D012097:Repressor Proteins / Q000737:chemistry / Q000378:metabolism*; D012160:Retina / Q000187:drug effects / Q000473:pathology
chemical_list: D029721:Drosophila Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D010455:Peptides; D012097:Repressor Proteins; C097188:polyglutamine; C092341:ATXN3 protein, human; D000067699:Ataxin-3