Large-scale screen for modifiers of ataxin-3-derived polyglutamine-induced toxicity in Drosophila

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 exten...

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Bibliographic Details
Published in:PloS one 2012-11, Vol.7 (11), p.e47452
Main Authors: VoSSfeldt, Hannes, Butzlaff, Malte, PrüSSing, Katja, Ní Chárthaigh, Róisín-Ana, Karsten, Peter, Lankes, Anne, Hamm, Sabine, Simons, Mikael, Adryan, Boris, Schulz, Jörg B, Voigt, Aaron
Format: Article
Language:English
Subjects:
Alzheimer's disease
Alzheimers disease
Analysis
Animals
Ataxia
Ataxin
Ataxin-3
Bioinformatics
Biology
Computational Biology
Disorders
Dissociation
Drosophila
Drosophila melanogaster - drug effects
Drosophila melanogaster - metabolism
Drosophila Proteins - chemistry
Drosophila Proteins - metabolism
Elongation
Genes
Genetic aspects
Insects
Medical screening
Models, Biological
Molecular modelling
Mutation
Nerve Tissue Proteins - chemistry
Nerve Tissue Proteins - metabolism
Nervous system diseases
Neurodegeneration
Neurology
Nuclear Proteins - chemistry
Nuclear Proteins - metabolism
Pathogenesis
Peptides - chemistry
Peptides - toxicity
Polyglutamine diseases
Protein Structure, Quaternary
Proteins
Repressor Proteins - chemistry
Repressor Proteins - metabolism
Retina - drug effects
Retina - pathology
RNA Interference
RNA-mediated interference
Toxicity
Trinucleotide repeat diseases
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Description
Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0047452