A carregar...
Publicação
Estudo da estabilidade da TTR após o transplante hepático em doentes PAF
| Nome: | Descrição: | Tamanho: | Formato: | |
|---|---|---|---|---|
| 3.04 MB | Adobe PDF |
Autores
Orientador(es)
Resumo(s)
A Polineuropatia Amiloidótica Familiar (PAF) é uma doença autossómica dominante progressiva caraterizada pela deposição de fibras amilóides formadas pela proteína Transtirretina (TTR). É uma patologia severa e que constitui um paradigma, uma vez que existem observações fenotípicas que sugerem um modelo de patogénese mais complexo do que a simples presença de mutações na cadeia polipeptídica da TTR. De modo a tentar compreender de que forma outros fatores não genéticos podem alterar a progressão desta doença, o presente trabalho apostou na análise de vários estados de progressão da PAF, para o qual se utilizou amostras de plasma de indivíduos portadores heterozigóticos da mutação V30M sintomáticos e indivíduos que sofreram um transplante de fígado cadáver. Foram avaliados os interactuantes da TTR e os níveis de glicação. O trabalho desenvolvido mostrou inequivocamente que o tempo de meia vida da TTR ronda os 3 dias, sendo que ao fim do sexto dia a variante mutada já foi totalmente substituída pela variante WT em indivíduos transplantados com fígado cadáver. Já os interactuantes da TTR identificados neste trabalho em pacientes PAF não transplantados foram a albumina, o retinol-binding protein, urocortino-3 e IgG1, sendo que a albumina e o retinol-binding protein já tinham sido descritos na literatura. Contudo, nos pacientes transplantados e monitorizados estavam apenas presentes a albumina, a IgG1 e o urocortino-3. A execução deste trabalho permite reforçar o envolvimento de fatores não genéticos no modelo de patogénese da PAF, nomeadamente um modelo multifatorial.
Familial Amyloid Polyneuropathy (FAP) is a progressive autosomal dominant disease characterized by the deposition of amyloid fibrils formed by the protein transthyretin (TTR). It is a severe disease and it is a paradigm, since there are phenotypic observations which suggest a more complex model of pathogenesis, with more than the presence of mutations in the polypeptide chain of TTR. In order to try to understand how other non-genetic factors can alter the progression of this disease, this study bet on the analysis of various progression states of PAF, for which was used plasma samples from heterozygous carries of V30M mutation with symptoms and individuals who have undergone a liver transplant. We evaluated the moleculs that interact with TTR and glycation levels. The work clearly showed that the half-life of TTR was around 3 days, and at the end of the sixth day the mutated variant has been completely replaced by the WT variant. The interacting molecules of TTR identified in this study in non-transplanted PAF patients were albumin, retinol-binding protein, urocortino-3 and IgG1, wherein the albumin and retinol-binding protein were already described in the literature. However, in transplanted patients were present only albumin, IgG1 and urocortino-3. The execution of this work reinforces the involvement of non-genetic factor in the pathogenesis modelo f FAP.
Familial Amyloid Polyneuropathy (FAP) is a progressive autosomal dominant disease characterized by the deposition of amyloid fibrils formed by the protein transthyretin (TTR). It is a severe disease and it is a paradigm, since there are phenotypic observations which suggest a more complex model of pathogenesis, with more than the presence of mutations in the polypeptide chain of TTR. In order to try to understand how other non-genetic factors can alter the progression of this disease, this study bet on the analysis of various progression states of PAF, for which was used plasma samples from heterozygous carries of V30M mutation with symptoms and individuals who have undergone a liver transplant. We evaluated the moleculs that interact with TTR and glycation levels. The work clearly showed that the half-life of TTR was around 3 days, and at the end of the sixth day the mutated variant has been completely replaced by the WT variant. The interacting molecules of TTR identified in this study in non-transplanted PAF patients were albumin, retinol-binding protein, urocortino-3 and IgG1, wherein the albumin and retinol-binding protein were already described in the literature. However, in transplanted patients were present only albumin, IgG1 and urocortino-3. The execution of this work reinforces the involvement of non-genetic factor in the pathogenesis modelo f FAP.
Descrição
Tese de mestrado, Bioquímica, Universidade de Lisboa, Faculdade de Ciências, 2016
Palavras-chave
Polineuropatia amiloidótica familiar Transtirretina V30M Interactuantes Glicação Teses de mestrado - 2016