Lithium chloride therapy fails to improve motor function in a transgenic mouse model of Machado-Joseph disease
Autor(a) principal: | |
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Data de Publicação: | 2014 |
Outros Autores: | , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/1822/33268 |
Resumo: | The accumulation of misfolded proteins in neurons, leading to the formation of cytoplasmic and nuclear aggregates, is a common theme in age-related neurodegenerative diseases, possibly due to disturbances of the proteostasis and insufficient activity of cellular protein clearance pathways. Lithium is a well-known autophagy inducer that exerts neuroprotective effects in different conditions and has been proposed as a promising therapeutic agent for several neurodegenerative diseases. We tested the efficacy of chronic lithium 10.4 mg/kg) treatment in a transgenic mouse model of Machado-Joseph disease, an inherited neurodegenerative disease, caused by an expansion of a polyglutamine tract within the protein ataxin-3. A battery of behavioral tests was used to assess disease progression. In spite of activating autophagy, as suggested by the increased levels of Beclin-1, Atg7, and LC3II, and a reduction in the p62 protein levels, lithium administration showed no overall beneficial effects in this model concerning motor performance, showing a positive impact only in the reduction of tremors at 24 weeks of age. Our results do not support lithiumchronic treatment as a promising strategy for the treatment of Machado-Joseph disease (MJD). |
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Lithium chloride therapy fails to improve motor function in a transgenic mouse model of Machado-Joseph diseaseAutophagyLithiumPolyglutamineSpinocerebellar ataxiaTherapyTriplet repeatsScience & TechnologyThe accumulation of misfolded proteins in neurons, leading to the formation of cytoplasmic and nuclear aggregates, is a common theme in age-related neurodegenerative diseases, possibly due to disturbances of the proteostasis and insufficient activity of cellular protein clearance pathways. Lithium is a well-known autophagy inducer that exerts neuroprotective effects in different conditions and has been proposed as a promising therapeutic agent for several neurodegenerative diseases. We tested the efficacy of chronic lithium 10.4 mg/kg) treatment in a transgenic mouse model of Machado-Joseph disease, an inherited neurodegenerative disease, caused by an expansion of a polyglutamine tract within the protein ataxin-3. A battery of behavioral tests was used to assess disease progression. In spite of activating autophagy, as suggested by the increased levels of Beclin-1, Atg7, and LC3II, and a reduction in the p62 protein levels, lithium administration showed no overall beneficial effects in this model concerning motor performance, showing a positive impact only in the reduction of tremors at 24 weeks of age. Our results do not support lithiumchronic treatment as a promising strategy for the treatment of Machado-Joseph disease (MJD).FCT -Fundação para a Ciência e a Tecnologia(SFRH/BD/51059/2010)SpringerUniversidade do MinhoSilva, Sara DuarteCarvalho, Andreia NevesCunha, Carina SoaresCastro, Andreia Cristiana Teixeira deOliveira, PedroFernandes, Anabela SilvaMaciel, P.20142014-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/33268eng1473-422210.1007/s12311-014-0589-925112410http://link.springer.cominfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-21T12:04:10Zoai:repositorium.sdum.uminho.pt:1822/33268Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T18:54:24.087200Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Lithium chloride therapy fails to improve motor function in a transgenic mouse model of Machado-Joseph disease |
title |
Lithium chloride therapy fails to improve motor function in a transgenic mouse model of Machado-Joseph disease |
spellingShingle |
Lithium chloride therapy fails to improve motor function in a transgenic mouse model of Machado-Joseph disease Silva, Sara Duarte Autophagy Lithium Polyglutamine Spinocerebellar ataxia Therapy Triplet repeats Science & Technology |
title_short |
Lithium chloride therapy fails to improve motor function in a transgenic mouse model of Machado-Joseph disease |
title_full |
Lithium chloride therapy fails to improve motor function in a transgenic mouse model of Machado-Joseph disease |
title_fullStr |
Lithium chloride therapy fails to improve motor function in a transgenic mouse model of Machado-Joseph disease |
title_full_unstemmed |
Lithium chloride therapy fails to improve motor function in a transgenic mouse model of Machado-Joseph disease |
title_sort |
Lithium chloride therapy fails to improve motor function in a transgenic mouse model of Machado-Joseph disease |
author |
Silva, Sara Duarte |
author_facet |
Silva, Sara Duarte Carvalho, Andreia Neves Cunha, Carina Soares Castro, Andreia Cristiana Teixeira de Oliveira, Pedro Fernandes, Anabela Silva Maciel, P. |
author_role |
author |
author2 |
Carvalho, Andreia Neves Cunha, Carina Soares Castro, Andreia Cristiana Teixeira de Oliveira, Pedro Fernandes, Anabela Silva Maciel, P. |
author2_role |
author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade do Minho |
dc.contributor.author.fl_str_mv |
Silva, Sara Duarte Carvalho, Andreia Neves Cunha, Carina Soares Castro, Andreia Cristiana Teixeira de Oliveira, Pedro Fernandes, Anabela Silva Maciel, P. |
dc.subject.por.fl_str_mv |
Autophagy Lithium Polyglutamine Spinocerebellar ataxia Therapy Triplet repeats Science & Technology |
topic |
Autophagy Lithium Polyglutamine Spinocerebellar ataxia Therapy Triplet repeats Science & Technology |
description |
The accumulation of misfolded proteins in neurons, leading to the formation of cytoplasmic and nuclear aggregates, is a common theme in age-related neurodegenerative diseases, possibly due to disturbances of the proteostasis and insufficient activity of cellular protein clearance pathways. Lithium is a well-known autophagy inducer that exerts neuroprotective effects in different conditions and has been proposed as a promising therapeutic agent for several neurodegenerative diseases. We tested the efficacy of chronic lithium 10.4 mg/kg) treatment in a transgenic mouse model of Machado-Joseph disease, an inherited neurodegenerative disease, caused by an expansion of a polyglutamine tract within the protein ataxin-3. A battery of behavioral tests was used to assess disease progression. In spite of activating autophagy, as suggested by the increased levels of Beclin-1, Atg7, and LC3II, and a reduction in the p62 protein levels, lithium administration showed no overall beneficial effects in this model concerning motor performance, showing a positive impact only in the reduction of tremors at 24 weeks of age. Our results do not support lithiumchronic treatment as a promising strategy for the treatment of Machado-Joseph disease (MJD). |
publishDate |
2014 |
dc.date.none.fl_str_mv |
2014 2014-01-01T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/1822/33268 |
url |
http://hdl.handle.net/1822/33268 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
1473-4222 10.1007/s12311-014-0589-9 25112410 http://link.springer.com |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Springer |
publisher.none.fl_str_mv |
Springer |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
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1799132326043582464 |