Utilize este identificador para referenciar este registo:
https://hdl.handle.net/1822/18788
Título: | Neuron-specific proteotoxicity of mutant ataxin-3 in C. elegans: rescue by the DAF-16 and HSF-1 pathways |
Autor(es): | 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. |
Data: | 1-Ago-2011 |
Editora: | Oxford University Press |
Revista: | Human Molecular Genetics |
Resumo(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. |
Tipo: | Artigo |
URI: | https://hdl.handle.net/1822/18788 |
DOI: | 10.1093/hmg/ddr203 |
ISSN: | 0964-6906 |
Versão da editora: | http://hmg.oxfordjournals.org |
Arbitragem científica: | yes |
Acesso: | Acesso aberto |
Aparece nas coleções: | ICVS - Artigos em revistas internacionais / Papers in international journals |
Ficheiros deste registo:
Ficheiro | Descrição | Tamanho | Formato | |
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Teixeira-Castro A_Hum Mol Genet-posp 2011.pdf | versão posprint | 735,88 kB | Adobe PDF | Ver/Abrir |