Avaliação dos efeitos da rutina em modelo de doença de Huntington em Caenorhabditis elegans
Autor(a) principal: | |
---|---|
Data de Publicação: | 2019 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Manancial - Repositório Digital da UFSM |
Texto Completo: | http://repositorio.ufsm.br/handle/1/21402 |
Resumo: | Huntington's disease (DH) is a progressive and hereditary neurodegenerative disorder predominantly caused by the expansion of a CAG repeat, which encodes polyglutamine (polyQ). This pathology results in loss of neuronal cells, motor alterations, dementia and is currently a disease without cure. The rutin is a flavonoid found in plants such as Passiflora incarnata, buckwheat, some teas and also in apples. It is known to have antioxidant, cytoprotective, anticancer and neuroprotective activities. Thus, we investigated the effect of in vivo rutin chronic exposure on the DH model using transgenic lines of the nematode Caenorhabditis elegans. The C elegans is a small nematode (± 1 mm), easy to handle, short life cycle, easy to grow and fast generation time. The animals were treated from the L1 stage with 15, 30, 60 and 120 μM rutin until adulthood. We evaluated behavioral assays, polyQ aggregation, oxidative damage, neurodegeneration level, lifespan, and investigated the possible role of autophagy and insulin / IGF1 (IIS) signaling pathways in the beneficial effects induced by the rutin. In general, our data demonstrate that routine treatment reduced polyglutamine (polyQ) protein aggregation in muscle, reduced polyQ mediated neuronal death in ASH sensory neurons, and extended lifespan in C. elegans. The possible mechanisms involved in the actions described are: antioxidant activity per se of the extract, activation of protein degradation (autophagy), and insulin / IGF1 (IIS) signaling pathways. These findings demonstrate that chronic exposure to rutin may play a useful role in the prevention of DH and also provide possible avenues to be explored for the search for new therapies against aging-related proteinopathies. |
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2021-07-13T10:55:09Z2021-07-13T10:55:09Z2019-07-19http://repositorio.ufsm.br/handle/1/21402Huntington's disease (DH) is a progressive and hereditary neurodegenerative disorder predominantly caused by the expansion of a CAG repeat, which encodes polyglutamine (polyQ). This pathology results in loss of neuronal cells, motor alterations, dementia and is currently a disease without cure. The rutin is a flavonoid found in plants such as Passiflora incarnata, buckwheat, some teas and also in apples. It is known to have antioxidant, cytoprotective, anticancer and neuroprotective activities. Thus, we investigated the effect of in vivo rutin chronic exposure on the DH model using transgenic lines of the nematode Caenorhabditis elegans. The C elegans is a small nematode (± 1 mm), easy to handle, short life cycle, easy to grow and fast generation time. The animals were treated from the L1 stage with 15, 30, 60 and 120 μM rutin until adulthood. We evaluated behavioral assays, polyQ aggregation, oxidative damage, neurodegeneration level, lifespan, and investigated the possible role of autophagy and insulin / IGF1 (IIS) signaling pathways in the beneficial effects induced by the rutin. In general, our data demonstrate that routine treatment reduced polyglutamine (polyQ) protein aggregation in muscle, reduced polyQ mediated neuronal death in ASH sensory neurons, and extended lifespan in C. elegans. The possible mechanisms involved in the actions described are: antioxidant activity per se of the extract, activation of protein degradation (autophagy), and insulin / IGF1 (IIS) signaling pathways. These findings demonstrate that chronic exposure to rutin may play a useful role in the prevention of DH and also provide possible avenues to be explored for the search for new therapies against aging-related proteinopathies.A doença de Huntington (DH) é um transtorno neurodegenerativo progressivo e hereditário predominantemente causado pela expansão de uma repetição CAG, que codifica a poliglutamina (poliQ). Essa patologia resulta em perda de células neuronais, alterações motoras, demência e atualmente é uma doença sem cura. A rutina é um flavonoide encontrado em plantas, como Passiflora incarnata, trigo sarraceno, alguns chás e também em maçãs. Ela é conhecida por possuir atividades antioxidantes, citoprotetoras, anticancerígena e neuroprotetoras. Assim, nós investigamos o efeito da exposição crônica de rutina in vivo no modelo de DH utilizando linhagens transgênicas do nematoide Caenorhabditis elegans. O C elegans é um nematódeo pequeno (±1 mm), de fácil manipulação, curto ciclo de vida, fácil de cultivo e rápido tempo de geração. Os animais foram tratados a partir do estágio L1 com 15, 30, 60 e 120 μM de rutina até a idade adulta. Avaliamos ensaios comportamentais, a agregação poliQ, o dano oxidativo, o nível de neurodegeneração, o tempo de vida e investigamos o possível papel das vias de sinalização da autofagia e da insulina / IGF1 (IIS) nos efeitos benéficos induzidos pela rutina. Em geral, nossos dados demonstram que o tratamento com rutina reduziu a agregação da proteína poliglutamina (poliQ) no músculo, reduziu a morte neuronal mediada por poliQ em neurônios sensoriais de ASH e prolongou a vida útil em C. elegans. Os possíveis mecanismos envolvidos nas ações descritas são: atividade antioxidante per se do extrato, ativação da degradação proteica (autofagia), e ainda as vias de sinalização da insulina / IGF1 (IIS). Esses achados demonstram que a exposição crônica a rutina pode desempenhar um papel útil na prevenção da DH e também fornecer possíveis caminhos a serem explorados para a busca de novas terapias contra as proteinopatias relacionadas ao envelhecimento.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESporUniversidade Federal de Santa MariaCentro de Ciências Naturais e ExatasPrograma de Pós-Graduação em Ciências Biológicas: Bioquímica ToxicológicaUFSMBrasilBioquímicaAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessDoença de HuntingtonCNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICAAvaliação dos efeitos da rutina em modelo de doença de Huntington em Caenorhabditis elegansEvaluation of rutin effects in a Huntington disease model in Caenorhabditis elegansinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisSoares, Félix Alexandre Antuneshttp://lattes.cnpq.br/8752453650114092Chitolina, Maria RosaPerin, Rosilene Rodrigues Kaizerhttp://lattes.cnpq.br/9646328956877026Cordeiro, Larissa Marafiga2008000000026006006006006003aef53b7-b173-4c56-a944-bed2de5e5ddaf5950a75-7ceb-45b8-a15e-d0bf5f1b423661e17a1f-d519-4f2d-988e-a5c6b35eb0a618600afd-4b2d-4be6-86fa-faaa3e1b1043reponame:Manancial - Repositório Digital da UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMORIGINALDIS_PPGCBBT_2019_CORDEIRO_LARISSA.pdfDIS_PPGCBBT_2019_CORDEIRO_LARISSA.pdfDissertaçãoapplication/pdf1934209http://repositorio.ufsm.br/bitstream/1/21402/1/DIS_PPGCBBT_2019_CORDEIRO_LARISSA.pdf2b899ac398905a318997350e9053a359MD51CC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; 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dc.title.por.fl_str_mv |
Avaliação dos efeitos da rutina em modelo de doença de Huntington em Caenorhabditis elegans |
dc.title.alternative.eng.fl_str_mv |
Evaluation of rutin effects in a Huntington disease model in Caenorhabditis elegans |
title |
Avaliação dos efeitos da rutina em modelo de doença de Huntington em Caenorhabditis elegans |
spellingShingle |
Avaliação dos efeitos da rutina em modelo de doença de Huntington em Caenorhabditis elegans Cordeiro, Larissa Marafiga Doença de Huntington CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
title_short |
Avaliação dos efeitos da rutina em modelo de doença de Huntington em Caenorhabditis elegans |
title_full |
Avaliação dos efeitos da rutina em modelo de doença de Huntington em Caenorhabditis elegans |
title_fullStr |
Avaliação dos efeitos da rutina em modelo de doença de Huntington em Caenorhabditis elegans |
title_full_unstemmed |
Avaliação dos efeitos da rutina em modelo de doença de Huntington em Caenorhabditis elegans |
title_sort |
Avaliação dos efeitos da rutina em modelo de doença de Huntington em Caenorhabditis elegans |
author |
Cordeiro, Larissa Marafiga |
author_facet |
Cordeiro, Larissa Marafiga |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Soares, Félix Alexandre Antunes |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/8752453650114092 |
dc.contributor.referee1.fl_str_mv |
Chitolina, Maria Rosa |
dc.contributor.referee2.fl_str_mv |
Perin, Rosilene Rodrigues Kaizer |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/9646328956877026 |
dc.contributor.author.fl_str_mv |
Cordeiro, Larissa Marafiga |
contributor_str_mv |
Soares, Félix Alexandre Antunes Chitolina, Maria Rosa Perin, Rosilene Rodrigues Kaizer |
dc.subject.por.fl_str_mv |
Doença de Huntington |
topic |
Doença de Huntington CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
description |
Huntington's disease (DH) is a progressive and hereditary neurodegenerative disorder predominantly caused by the expansion of a CAG repeat, which encodes polyglutamine (polyQ). This pathology results in loss of neuronal cells, motor alterations, dementia and is currently a disease without cure. The rutin is a flavonoid found in plants such as Passiflora incarnata, buckwheat, some teas and also in apples. It is known to have antioxidant, cytoprotective, anticancer and neuroprotective activities. Thus, we investigated the effect of in vivo rutin chronic exposure on the DH model using transgenic lines of the nematode Caenorhabditis elegans. The C elegans is a small nematode (± 1 mm), easy to handle, short life cycle, easy to grow and fast generation time. The animals were treated from the L1 stage with 15, 30, 60 and 120 μM rutin until adulthood. We evaluated behavioral assays, polyQ aggregation, oxidative damage, neurodegeneration level, lifespan, and investigated the possible role of autophagy and insulin / IGF1 (IIS) signaling pathways in the beneficial effects induced by the rutin. In general, our data demonstrate that routine treatment reduced polyglutamine (polyQ) protein aggregation in muscle, reduced polyQ mediated neuronal death in ASH sensory neurons, and extended lifespan in C. elegans. The possible mechanisms involved in the actions described are: antioxidant activity per se of the extract, activation of protein degradation (autophagy), and insulin / IGF1 (IIS) signaling pathways. These findings demonstrate that chronic exposure to rutin may play a useful role in the prevention of DH and also provide possible avenues to be explored for the search for new therapies against aging-related proteinopathies. |
publishDate |
2019 |
dc.date.issued.fl_str_mv |
2019-07-19 |
dc.date.accessioned.fl_str_mv |
2021-07-13T10:55:09Z |
dc.date.available.fl_str_mv |
2021-07-13T10:55:09Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
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masterThesis |
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publishedVersion |
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http://repositorio.ufsm.br/handle/1/21402 |
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http://repositorio.ufsm.br/handle/1/21402 |
dc.language.iso.fl_str_mv |
por |
language |
por |
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200800000002 |
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600 600 600 600 600 |
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Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess |
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Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Centro de Ciências Naturais e Exatas |
dc.publisher.program.fl_str_mv |
Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica |
dc.publisher.initials.fl_str_mv |
UFSM |
dc.publisher.country.fl_str_mv |
Brasil |
dc.publisher.department.fl_str_mv |
Bioquímica |
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Universidade Federal de Santa Maria Centro de Ciências Naturais e Exatas |
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