Synaptosomal signal transduction in Alzheimer's disease
Autor(a) principal: | |
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Data de Publicação: | 2011 |
Tipo de documento: | Dissertação |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10773/7418 |
Resumo: | Alzheimer’s Disease (AD) is characterized by the presence of amyloid plaques (APs) and neurofibrillary tangles (NFTs), which consist of Abeta aggregates and hyperphosphorylated tau, respectively. It is known that increasing Abeta concentrations precede NFT production. Moreover, several lines of evidence suggest that the increase in APP and tau phosphorylation is the result of Abeta neurotoxicity. Although, the precise effects of the neurotoxic peptide on APP and tau phosphorylation remain yet to be fully elucidated. Synapses exhibit high concentrations of protein kinases (PKs) and protein phosphatases (PPs). Therefore, it is essential to adopt a model system that mimics what happens at the synapse. Synaptosomes are actually recognized as “in vitro synapses” and for that reason were the model system used. Our data revealed that there was a considerable enrichment of pre- and postsynaptic markers in the synaptosomal fraction after synaptosome isolation. Given these results, we went on to test the effects of Abeta on synaptosomal viability, which was found to be slightly decreased, confirming the high viability of synaptosomes. In addition, we observed the increase of APP and tau phosphorylation after Abeta treatment, while holo-APP and total tau levels were maintained, independently of Abeta concentrations. These results suggest that Abeta can actually induce APP and tau hyperphosphorylation. The conclusions attained from this dissertation are important to comprehend the pathways related to the pathogenesis of Alzheimer’s disease. |
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Synaptosomal signal transduction in Alzheimer's diseaseBiomedicinaDoença de AlzheimerProteínasFosforilaçãoAlzheimer’s Disease (AD) is characterized by the presence of amyloid plaques (APs) and neurofibrillary tangles (NFTs), which consist of Abeta aggregates and hyperphosphorylated tau, respectively. It is known that increasing Abeta concentrations precede NFT production. Moreover, several lines of evidence suggest that the increase in APP and tau phosphorylation is the result of Abeta neurotoxicity. Although, the precise effects of the neurotoxic peptide on APP and tau phosphorylation remain yet to be fully elucidated. Synapses exhibit high concentrations of protein kinases (PKs) and protein phosphatases (PPs). Therefore, it is essential to adopt a model system that mimics what happens at the synapse. Synaptosomes are actually recognized as “in vitro synapses” and for that reason were the model system used. Our data revealed that there was a considerable enrichment of pre- and postsynaptic markers in the synaptosomal fraction after synaptosome isolation. Given these results, we went on to test the effects of Abeta on synaptosomal viability, which was found to be slightly decreased, confirming the high viability of synaptosomes. In addition, we observed the increase of APP and tau phosphorylation after Abeta treatment, while holo-APP and total tau levels were maintained, independently of Abeta concentrations. These results suggest that Abeta can actually induce APP and tau hyperphosphorylation. The conclusions attained from this dissertation are important to comprehend the pathways related to the pathogenesis of Alzheimer’s disease.A doença de Alzheimer (DA) caracteriza-se pela presença de placas amilóides e de tranças neurofibrilares, que consistem em acumulações de Abeta e tau hiperfosforilada, respectivamente. Concentrações crescentes de Abeta precedem o aparecimento de tranças neurofibrilares. Além disso, vários estudos sugerem que o aumento da fosfoforilação da APP e da tau no decorrer da DA é consequência da neurotoxicidade do Abeta. No entanto, os efeitos específicos do Abeta na fosforilação da APP e da tau ainda não foram estabelecidos. Há grande abundância de cinases e fosfatases nas sinapses, sendo portanto fundamental adoptar um modelo de estudo que as mimetize. De facto, os sinaptossomas são actualmente reconhecidos como “sinapses in vitro”, e por esse motivo foram o modelo de estudo utilizado. Os dados obtidos mostraram um considerável enriquecimento de proteínas pré- e pós-sinápticas na fracção sinaptossomal, após o isolamento de sinaptossomas. Posto isto, testámos os efeitos do Abeta na viabilidade sinaptossomal, tendo-se observado a sua diminuição generalizada, o que confirma a toxicidade do péptido. Foi também observado o aumento da fosforilação da APP e da tau após o tratamento com Abeta, enquanto que os níveis de APP e tau totais permaneceram inalterados, independentemente das concentrações de Abeta. Estes resultados sugerem que o Abeta pode realmente induzir a hiperfosforilação da APP e da tau. As conclusões retiradas desta dissertação são importantes para compreender melhor as vias relacionadas com a patogénese da DA.Universidade de Aveiro2013-07-05T13:49:40Z2011-07-07T00:00:00Z2011-07-07info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://hdl.handle.net/10773/7418engCoelho, Edgar Duarte de Jesus Valente Marquesinfo: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:RCAAP2024-02-22T11:12:52Zoai:ria.ua.pt:10773/7418Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T02:45:06.325259Repositório 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 |
Synaptosomal signal transduction in Alzheimer's disease |
title |
Synaptosomal signal transduction in Alzheimer's disease |
spellingShingle |
Synaptosomal signal transduction in Alzheimer's disease Coelho, Edgar Duarte de Jesus Valente Marques Biomedicina Doença de Alzheimer Proteínas Fosforilação |
title_short |
Synaptosomal signal transduction in Alzheimer's disease |
title_full |
Synaptosomal signal transduction in Alzheimer's disease |
title_fullStr |
Synaptosomal signal transduction in Alzheimer's disease |
title_full_unstemmed |
Synaptosomal signal transduction in Alzheimer's disease |
title_sort |
Synaptosomal signal transduction in Alzheimer's disease |
author |
Coelho, Edgar Duarte de Jesus Valente Marques |
author_facet |
Coelho, Edgar Duarte de Jesus Valente Marques |
author_role |
author |
dc.contributor.author.fl_str_mv |
Coelho, Edgar Duarte de Jesus Valente Marques |
dc.subject.por.fl_str_mv |
Biomedicina Doença de Alzheimer Proteínas Fosforilação |
topic |
Biomedicina Doença de Alzheimer Proteínas Fosforilação |
description |
Alzheimer’s Disease (AD) is characterized by the presence of amyloid plaques (APs) and neurofibrillary tangles (NFTs), which consist of Abeta aggregates and hyperphosphorylated tau, respectively. It is known that increasing Abeta concentrations precede NFT production. Moreover, several lines of evidence suggest that the increase in APP and tau phosphorylation is the result of Abeta neurotoxicity. Although, the precise effects of the neurotoxic peptide on APP and tau phosphorylation remain yet to be fully elucidated. Synapses exhibit high concentrations of protein kinases (PKs) and protein phosphatases (PPs). Therefore, it is essential to adopt a model system that mimics what happens at the synapse. Synaptosomes are actually recognized as “in vitro synapses” and for that reason were the model system used. Our data revealed that there was a considerable enrichment of pre- and postsynaptic markers in the synaptosomal fraction after synaptosome isolation. Given these results, we went on to test the effects of Abeta on synaptosomal viability, which was found to be slightly decreased, confirming the high viability of synaptosomes. In addition, we observed the increase of APP and tau phosphorylation after Abeta treatment, while holo-APP and total tau levels were maintained, independently of Abeta concentrations. These results suggest that Abeta can actually induce APP and tau hyperphosphorylation. The conclusions attained from this dissertation are important to comprehend the pathways related to the pathogenesis of Alzheimer’s disease. |
publishDate |
2011 |
dc.date.none.fl_str_mv |
2011-07-07T00:00:00Z 2011-07-07 2013-07-05T13:49:40Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
format |
masterThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10773/7418 |
url |
http://hdl.handle.net/10773/7418 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
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 |
Universidade de Aveiro |
publisher.none.fl_str_mv |
Universidade de Aveiro |
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 |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
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 |
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1799137503550111744 |