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- Title
Polyglutamine Atrophin provokes neurodegeneration in Drosophila by repressing fat.
- Authors
Napoletano, Francesco; Occhi, Simona; Calamita, Piera; Volpi, Vera; Blanc, Eric; Charroux, Bernard; Royet, Julien; Fanto, Manolis
- Abstract
Large alterations in transcription accompany neurodegeneration in polyglutamine (polyQ) diseases. These pathologies manifest both general polyQ toxicity and mutant protein-specific effects. In this study, we report that the fat tumour suppressor gene mediates neurodegeneration induced by the polyQ protein Atrophin. We have monitored early transcriptional alterations in a Drosophila model of Dentatorubral-pallidoluysian Atrophy and found that polyQ Atrophins downregulate fat. Fat protects from neurodegeneration and Atrophin toxicity through the Hippo kinase cascade. Fat/Hippo signalling does not provoke neurodegeneration by stimulating overgrowth; rather, it alters the autophagic flux in photoreceptor neurons, thereby affecting cell homeostasis. Our data thus provide a crucial insight into the specific mechanism of a polyQ disease and reveal an unexpected neuroprotective role of the Fat/Hippo pathway.
- Publication
The EMBO journal, 2011, Vol 30, Issue 5, p945
- ISSN
1460-2075
- Publication type
Journal Article
- DOI
10.1038/emboj.2011.1