Please use this identifier to cite or link to this item:

TitleNeuron-specific proteotoxicity of mutant ataxin-3 in C. elegans: rescue by the DAF-16 and HSF-1 pathways
Author(s)Castro, Andreia Cristiana Teixeira de
Ailion, Michael
Jalles, Ana
Brignull, Heather
Vilaça, João L.
Dias, N. S.
Rodrigues, Pedro L.
Oliveira, João F.
Neves-Carvalho, Andreia
Morimoto, Richard
Maciel, P.
Issue date1-Aug-2011
PublisherOxford University Press
JournalHuman Molecular Genetics
Abstract(s)The risk of developing neurodegenerative diseases increases with age. Although many of the molecular pathways regulating proteotoxic stress and longevity are well characterized, their contribution to disease susceptibility remains unclear. In this study, we describe a new Caenorhabditis elegans model of Machado–Joseph disease pathogenesis. Pan-neuronal expression of mutant ATXN3 leads to a polyQ-length dependent, neuron subtype-specific aggregation and neuronal dysfunction. Analysis of different neurons revealed a pattern of dorsal nerve cord and sensory neuron susceptibility to mutant ataxin-3 that was distinct from the aggregation and toxicity profiles of polyQ-alone proteins. This reveals that the sequences flanking the polyQ-stretch in ATXN3 have a dominant influence on cell-intrinsic neuronal factors that modulate polyQ-mediated athogenesis. Aging influences the ATXN3 phenotypes which can be suppressed by the nregulation of the insulin/insulin growth factor-1-like signaling pathway and activation of heat shock factor-1.
Publisher version
AccessOpen access
Appears in Collections:ICVS - Artigos em revistas internacionais / Papers in international journals

Files in This Item:
File Description SizeFormat 
Teixeira-Castro A_Hum Mol Genet-posp 2011.pdfversão posprint735,88 kBAdobe PDFView/Open

Partilhe no FacebookPartilhe no TwitterPartilhe no DeliciousPartilhe no LinkedInPartilhe no DiggAdicionar ao Google BookmarksPartilhe no MySpacePartilhe no Orkut
Exporte no formato BibTex mendeley Exporte no formato Endnote Adicione ao seu ORCID