Large-Scale Screen for Modifiers of Ataxin-3-Derived Polyglutamine-Induced Toxicity in Drosophila

被引：27

作者：

Vossfeldt, Hannes ^{[1
]}

Butzlaff, Malte ^{[1
]}

Pruessing, Katja ^{[1
]}

Charthaigh, Roisin-Ana Ni ^{[1
,4
]}

Karsten, Peter ^{[1
]}

Lankes, Anne ^{[1
]}

Hamm, Sabine ^{[1
]}

Simons, Mikael ^{[2
,3
]}

Adryan, Boris ^{[4
]}

Schulz, Joerg B. ^{[1
,5
]}

Voigt, Aaron ^{[1
]}

机构：

[1] Rhein Westfal TH Aachen, Dept Neurol, Univ Med Ctr, Aachen, Germany

[2] Max Planck Inst Expt Med, D-37075 Gottingen, Germany

[3] Univ Gottingen, Dept Neurol, D-3400 Gottingen, Germany

[4] Univ Cambridge, Cambridge Syst Biol Ctr, Cambridge, England

[5] Julich Aachen Res Alliance JARA Brain Translat Br, Aachen, Germany

来源：

PLOS ONE | 2012年 / 7卷 / 11期

关键词：

RNA INTERFERENCE SCREEN; INTRANUCLEAR INCLUSIONS; PROTEIN AGGREGATION; HUNTINGTONS-DISEASE; NUCLEAR-LOCALIZATION; REPEAT EXPANSION; TRANSGENIC MICE; NEURODEGENERATION; PROTEASOME; GENE;

D O I：

10.1371/journal.pone.0047452

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：9

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