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Modificações pós-traducionais de proteínas na amiloidogénese: glicação e agregação da transtirretina in vivo em saccharomyces cerevisiae
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Orientador(es)
Resumo(s)
As doenças amiloidóticas, como Alzheimer ou Parkinson, caracterizam-se pela deposição de agregados proteícos com propriedades estruturais características. Os mecanismos de formação destes depósitos são ainda pouco conhecidos bem como o seu papel na evolução patológica. Neste estudo, foram investigados alguns aspectos fundamentais no processo de amiloidogénese in vivo utilizando a transtiretina humana, envolvida na polineuropatia amiloidótica familiar. A transtiretina e mutantes amiloidogénicos foram expressos em Saccharomyces cerevisiae, um tubo de ensaio vivo, de modo a investigar a formação de fibras amilóides in vivo. Observou-se a formação de fibras amilóides in vivo, tendo sido desenvolvido um novo método analítico para investigar a sua formação. Foi assim possível verificar que o stress carbonílico potencia a formação de fibras amilóides e a sua toxicidade celular in vivo
The amyloid diseases, such as Alzheimer's or Parkinson's disease, are characterized by the abnormal accumulation of protein aggregates with specific structural properties. The underlying mechanisms of formation of these deposits are still mostly unknown, as well as their role on pathologic evolution. In the present work, fundamental aspects of in vivo amyloidogenesis involved in Familial Amyloidotic Polyneuropathy were studied, using human transthyretin. The native transthyretin and amiloidogenic variants were expressed in Saccharomyces cerevisiae, as a living test tube, in order to better study in vivo formation of amyloid fibrils. In vivo formation of amyloid fibrils was observed and a new analytic method to investigate its formation was developed. It was also possible to verify a correlation between carbonilic stress and amyloid fibril formation, as well as their toxicity to the living cells
The amyloid diseases, such as Alzheimer's or Parkinson's disease, are characterized by the abnormal accumulation of protein aggregates with specific structural properties. The underlying mechanisms of formation of these deposits are still mostly unknown, as well as their role on pathologic evolution. In the present work, fundamental aspects of in vivo amyloidogenesis involved in Familial Amyloidotic Polyneuropathy were studied, using human transthyretin. The native transthyretin and amiloidogenic variants were expressed in Saccharomyces cerevisiae, as a living test tube, in order to better study in vivo formation of amyloid fibrils. In vivo formation of amyloid fibrils was observed and a new analytic method to investigate its formation was developed. It was also possible to verify a correlation between carbonilic stress and amyloid fibril formation, as well as their toxicity to the living cells
Descrição
Tese de mestrado, Biologia (Biologia Celular e Biotecnologia), 2008, Universidade de Lisboa, Faculdade de Ciências
Palavras-chave
Biologia celular Amiloidose Teses de mestrado