Please use this identifier to cite or link to this item:
https://hdl.handle.net/10316/28131
DC Field | Value | Language |
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dc.contributor.author | Simões, Ana Teresa | - |
dc.contributor.author | Gonçalves, Nélio | - |
dc.contributor.author | Nobre, Rui Jorge | - |
dc.contributor.author | Duarte, Carlos Bandeira | - |
dc.contributor.author | Almeida, Luís Pereira de | - |
dc.date.accessioned | 2015-01-26T17:02:44Z | - |
dc.date.available | 2015-07-26T02:00:09Z | - |
dc.date.issued | 2014 | - |
dc.identifier.citation | SIMÕES, Ana Teresa; GONÇALVES, Nélio; NOBRE, Rui Jorge, DUARTE, Carlos Bandeira; ALMEIDA, Luís Pereira de - Calpain inhibition reduces ataxin-3 cleavage alleviating neuropathology and motor impairments in mouse models of Machado-Joseph disease. “Human Molecular Genetics”. ISSN: 0964-6906. 23:18 (2014) 4932–4944. Doi: 10.1093/hmg/ddu209>. | por |
dc.identifier.issn | 0964-6906 | - |
dc.identifier.uri | https://hdl.handle.net/10316/28131 | - |
dc.description.abstract | Machado–Joseph Disease (MJD) is the most prevalent autosomal dominantly inherited cerebellar ataxia. It is caused by an expanded CAG repeat in the ATXN3 gene, which translates into a polyglutamine tract within the ataxin-3 protein. Present treatments are symptomatic and do not prevent disease progression. As calpain overactivation has been shown to contribute to mutant ataxin-3 proteolysis, translocation to the nucleus, inclusions formation and neurodegeneration, we investigated the potential role of calpain inhibition as a therapeutic strategy to alleviate MJD pathology. For this purpose, we administered orally the calpain inhibitor BDA-410 to a lentiviral mouse model of MJD. Western-blot and immunohistochemical analysis revealed the presence of N- and C-terminal mutant ataxin-3 fragments and the colocalization of large inclusions with cleaved caspase-3 in the mice brain. Oral administration of the calpain inhibitor BDA-410 decreased both fragments formation and full-length ataxin-3 levels, reduced aggregation of mutant ataxin-3 and prevented cell injury and striatal and cerebellar degeneration. Importantly, in correlation with the preserved cerebellar morphology, BDA-410 prevented motor behavioural deficits. In conclusion, BDA-410 alleviates Machado–Joseph neuropathology and may therefore be an effective therapeutic option for MJD. | por |
dc.language.iso | eng | por |
dc.publisher | Oxford University Press | por |
dc.rights | embargoedAccess | por |
dc.title | Calpain inhibition reduces ataxin-3 cleavage alleviating neuropathology and motor impairments in mouse models of Machado-Joseph disease | por |
dc.type | article | por |
degois.publication.firstPage | 4932 | por |
degois.publication.lastPage | 4944 | por |
degois.publication.issue | 18 | por |
degois.publication.location | Oxford | por |
degois.publication.title | Human Molecular Genetics | por |
dc.relation.publisherversion | doi: 10.1093/hmg/ddu209 | por |
dc.peerreviewed | Yes | por |
dc.identifier.doi | 10.1093/hmg/ddu209 | - |
degois.publication.volume | 23 | por |
uc.controloAutoridade | Sim | - |
item.openairetype | article | - |
item.cerifentitytype | Publications | - |
item.languageiso639-1 | en | - |
item.fulltext | Com Texto completo | - |
item.grantfulltext | open | - |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
crisitem.author.researchunit | CNC - Center for Neuroscience and Cell Biology | - |
crisitem.author.researchunit | CNC - Center for Neuroscience and Cell Biology | - |
crisitem.author.researchunit | CNC - Center for Neuroscience and Cell Biology | - |
crisitem.author.researchunit | CIBB - Center for Innovative Biomedicine and Biotechnology | - |
crisitem.author.orcid | 0000-0003-3305-485X | - |
crisitem.author.orcid | 0000-0001-5816-2051 | - |
crisitem.author.orcid | 0000-0002-1474-0208 | - |
crisitem.author.orcid | 0000-0001-5831-3307 | - |
Appears in Collections: | FFUC- Artigos em Revistas Internacionais I&D CNC - Artigos em Revistas Internacionais FCTUC Ciências da Vida - Artigos em Revistas Internacionais |
Files in This Item:
File | Description | Size | Format | |
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14_HumMolGenet_Simões et al(1).pdf | 1.39 MB | Adobe PDF | View/Open |
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