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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Ataxin-3
-
Computational Biology
-
Drosophila Proteins / chemistry
-
Drosophila Proteins / metabolism*
-
Drosophila melanogaster / drug effects*
-
Drosophila melanogaster / metabolism*
-
Models, Biological
-
Nerve Tissue Proteins / chemistry
-
Nerve Tissue Proteins / metabolism*
-
Nuclear Proteins / chemistry
-
Nuclear Proteins / metabolism*
-
Peptides / chemistry
-
Peptides / toxicity*
-
Protein Structure, Quaternary
-
RNA Interference*
-
Repressor Proteins / chemistry
-
Repressor Proteins / metabolism*
-
Retina / drug effects
-
Retina / pathology
Substances
-
Drosophila Proteins
-
Nerve Tissue Proteins
-
Nuclear Proteins
-
Peptides
-
Repressor Proteins
-
polyglutamine
-
ATXN3 protein, human
-
Ataxin-3
Grants and funding
This work is/was funded by the “Bundesministerium für Bildung und Forschung” (“Nationales Genomforschungsnetz (NGFN+): 01GS08137/01GS08137-6a to AV and JBS and “Kompetenznetz Degenerative Demenzen” (KNDD): 01GI0703/01GI1005C to JBS). BA is a Royal Society University Research Fellow. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.