Publicação
Neuron-specific proteotoxicity of mutant ataxin-3 in C. elegans: rescue by the DAF-16 and HSF-1 pathways
| Resumo: | 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. |
|---|---|
| Autores principais: | Castro, Andreia Cristiana Teixeira de |
| Outros Autores: | 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. |
| Ano: | 2011 |
| País: | Portugal |
| Tipo de documento: | artigo |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade do Minho |
| Idioma: | inglês |
| Origem: | RepositóriUM - Universidade do Minho |
| _version_ | 1867439098483965952 |
|---|---|
| author | Castro, Andreia Cristiana Teixeira de |
| author2 | 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. |
| author2_role | author author author author author author author author author author |
| author_facet | 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. |
| author_role | author |
| contributor_name_str_mv | RepositóriUM - Universidade do Minho |
| country_str | PT |
| creators_json_txt | [{\"Person.name\":\"Castro, Andreia Cristiana Teixeira de\"},{\"Person.name\":\"Ailion, Michael\"},{\"Person.name\":\"Jalles, Ana\"},{\"Person.name\":\"Brignull, Heather\"},{\"Person.name\":\"Vilaça, João L.\"},{\"Person.name\":\"Dias, N. S.\"},{\"Person.name\":\"Rodrigues, Pedro L.\"},{\"Person.name\":\"Oliveira, João F.\"},{\"Person.name\":\"Neves-Carvalho, Andreia\"},{\"Person.name\":\"Morimoto, Richard\"},{\"Person.name\":\"Maciel, P.\"}] |
| datacite.contributors.contributor.contributorName.fl_str_mv | RepositóriUM - Universidade do Minho |
| datacite.creators.creator.creatorName.fl_str_mv | 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. |
| datacite.date.Accepted.fl_str_mv | 2011-08-01T00:00:00Z |
| datacite.date.available.fl_str_mv | 2012-04-20T11:46:22Z |
| datacite.date.embargoed.fl_str_mv | 2012-04-20T11:46:22Z |
| datacite.rights.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| datacite.titles.title.fl_str_mv | Neuron-specific proteotoxicity of mutant ataxin-3 in C. elegans: rescue by the DAF-16 and HSF-1 pathways |
| dc.contributor.none.fl_str_mv | RepositóriUM - Universidade do Minho |
| dc.creator.none.fl_str_mv | 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. |
| dc.date.Accepted.fl_str_mv | 2011-08-01T00:00:00Z |
| dc.date.available.fl_str_mv | 2012-04-20T11:46:22Z |
| dc.date.embargoed.fl_str_mv | 2012-04-20T11:46:22Z |
| dc.format.none.fl_str_mv | application/pdf |
| dc.identifier.none.fl_str_mv | https://hdl.handle.net/1822/18788 |
| dc.language.none.fl_str_mv | eng |
| dc.publisher.none.fl_str_mv | Oxford University Press |
| dc.rights.none.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| dc.title.fl_str_mv | Neuron-specific proteotoxicity of mutant ataxin-3 in C. elegans: rescue by the DAF-16 and HSF-1 pathways |
| dc.type.none.fl_str_mv | http://purl.org/coar/resource_type/c_6501 |
| description | 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. |
| dirty | 0 |
| eu_rights_str_mv | openAccess |
| format | article |
| fulltext.url.fl_str_mv | https://repositorium.uminho.pt/bitstreams/3609d9c6-2f15-4435-8f75-a4421fffe915/download |
| id | rum_8618b25d3fc7286e1e19ebd8d65ef7bc |
| identifier.url.fl_str_mv | https://hdl.handle.net/1822/18788 |
| instacron_str | repositorium |
| institution | Universidade do Minho |
| instname_str | Universidade do Minho |
| language | eng |
| network_acronym_str | rum |
| network_name_str | RepositóriUM - Universidade do Minho |
| oai_identifier_str | oai:repositorium.uminho.pt:1822/18788 |
| organization_str_mv | urn:organizationAcronym:repositorium |
| person_str_mv | 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. |
| publishDate | 2011 |
| publisher.none.fl_str_mv | Oxford University Press |
| reponame_str | RepositóriUM - Universidade do Minho |
| repository_id_str | urn:repositoryAcronym:rum |
| service_str_mv | urn:repositoryAcronym:rum |
| spelling | engOxford University PressporThe 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.application/pdfporNeuron-specific proteotoxicity of mutant ataxin-3 in C. elegans: rescue by the DAF-16 and HSF-1 pathwaysCastro, Andreia Cristiana Teixeira deAilion, MichaelJalles, AnaBrignull, HeatherVilaça, João L.Dias, N. S.Rodrigues, Pedro L.Oliveira, João F.Neves-Carvalho, AndreiaMorimoto, RichardMaciel, P.HostingInstitutionOrganizationalRepositóriUM - Universidade do Minhoe-mailmailto:repositorium@usdb.uminho.ptrepositorium@usdb.uminho.ptPMID21546381ISSNIsPartOf0964-6906DOIIsPartOf10.1093/hmg/ddr2032012-04-20T11:46:22Z2011-08-012011-08-01T00:00:00ZHandlehttps://hdl.handle.net/1822/18788http://purl.org/coar/access_right/c_abf2open access753544 bytesliteraturehttp://purl.org/coar/resource_type/c_6501journal articlehttp://purl.org/coar/access_right/c_abf2application/pdffulltexthttps://repositorium.uminho.pt/bitstreams/3609d9c6-2f15-4435-8f75-a4421fffe915/download |
| spellingShingle | Neuron-specific proteotoxicity of mutant ataxin-3 in C. elegans: rescue by the DAF-16 and HSF-1 pathways Castro, Andreia Cristiana Teixeira de |
| status | SINGLETON |
| title | Neuron-specific proteotoxicity of mutant ataxin-3 in C. elegans: rescue by the DAF-16 and HSF-1 pathways |
| title_full | Neuron-specific proteotoxicity of mutant ataxin-3 in C. elegans: rescue by the DAF-16 and HSF-1 pathways |
| title_fullStr | Neuron-specific proteotoxicity of mutant ataxin-3 in C. elegans: rescue by the DAF-16 and HSF-1 pathways |
| title_full_unstemmed | Neuron-specific proteotoxicity of mutant ataxin-3 in C. elegans: rescue by the DAF-16 and HSF-1 pathways |
| title_short | Neuron-specific proteotoxicity of mutant ataxin-3 in C. elegans: rescue by the DAF-16 and HSF-1 pathways |
| title_sort | Neuron-specific proteotoxicity of mutant ataxin-3 in C. elegans: rescue by the DAF-16 and HSF-1 pathways |
| url | https://hdl.handle.net/1822/18788 |
| visible | 1 |