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ProteĆ³mica da paramiloidose
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A Polineuropatia AmiloidĆ³tica Familiar (PAF) Ć© uma doenƧa neurodegenerativa, com manifestaƧƵes clĆnicas entre a terceira e a quarta dĆ©cada de vida, associada Ć deposiĆ§Ć£o de agregados amilĆ³ides de transtirretina (TTR) em diversos tecidos. A TTR Ć© produzida maioritariamente pelo fĆgado. A PAF estĆ” associada a mutaƧƵes pontuais na TTR, desestabilizadoras da sua estrutura tetramĆ©rica, levando Ć formaĆ§Ć£o de monĆ³meros sem a sua estrutura nativa. O diagnĆ³stico da PAF Ć© importante para a aplicaĆ§Ć£o de tratamentos adequados e atempados, e a pesquisa de biomarcadores prĆ©-sintomĆ”ticos Ć© vital. A saliva total Ć© um fluĆdo de diagnĆ³stico de confianƧa e Ć© utilizado para algumas doenƧas, por ser de recolha e anĆ”lise fĆ”ceis em relaĆ§Ć£o ao sangue, e pelo facto da saliva ter proteĆnas filtradas a partir do soro. As glĆ¢ndulas salivares em indivĆduos com PAF encontram-se infiltradas com depĆ³sitos de TTR, pelo que podem ocorrer alteraƧƵes a nĆvel do proteoma e de modificaƧƵes pĆ³s-traducionais, como a glicaĆ§Ć£o, que podem servir como biomarcadores. Neste trabalho, verificou-se que os perfis electroforĆ©ticos da saliva dos indivĆduos com PAF se encontram alterados. Foi possĆvel identificar proteĆnas que nĆ£o tinham sido identificadas antes na saliva, como a Ī±-sinucleĆna, sendo que esta mostra um perfil electroforĆ©tico, por si sĆ³, alterado. Estas eram maioritariamente filtradas a partir do soro. Por outro lado, foi observada uma expressĆ£o proteica diferencial na saliva dos indivĆduos com PAF, sendo que algumas das proteĆnas identificadas como diferenciadamente expressas, tambĆ©m se encontravam glicadas. A par destes resultados foi verificada a presenƧa de monĆ³meros de TTR em maior quantidade do que o seu tetrĆ¢mero, na saliva dos indivĆduos PAF. Finalmente, foi possĆvel a identificaĆ§Ć£o de proteĆnas expressas diferenciadamente na saliva de indivĆduos PAF, que podem ser utilizadas como biomarcadores para a PAF, podendo ser consideradas como eventuais biomarcadores prĆ©-sintomĆ”ticos.
Familial amyloidotic polyneuropathy is a neurodegenerative disease, with symptomatic manifestations between the third and fourth decade of life, related with amyloid deposition of transthyretin (TTR) in different tissues. TTR is mostly produced in the liver and in FAP is present with point mutations, which can destabilize the tetrameric native structure of this protein and lead to the formation of unfolded monomers. FAP diagnosis is a very important part of an adequate and prompt treatment, and the search of pre-symptomatic biomarkers is vital. The whole saliva is a reliable diagnostic fluid which is being used in some diseases, because itās easier to obtain and analyze than blood, and it has some proteins in common with serum, which were filtered from it. The salivary glands of FAP individuals contain TTR deposits that can influence the proteome and post-translational modifications, such as glycation, that can be used as biomarkers. In the present work we were able to observe distinct electrophoretic profiles in the saliva of FAP patients. We also identified new proteins in saliva, such as Ī±-synuclein, which also presented an altered electrophoretic profile. The identified proteins were mostly from serum. On the other hand, it was observed a differential expression of FAP proteins, some of those with glycated residues. Mean while, it was observed an higher percentage of TTR monomers than tetramers in FAP saliva. The identification of differentially expressed saliva proteins in FAP individuals, was accomplished, and these FAP biomarkers can be considered as pre-symptomatic biomarkers.
Familial amyloidotic polyneuropathy is a neurodegenerative disease, with symptomatic manifestations between the third and fourth decade of life, related with amyloid deposition of transthyretin (TTR) in different tissues. TTR is mostly produced in the liver and in FAP is present with point mutations, which can destabilize the tetrameric native structure of this protein and lead to the formation of unfolded monomers. FAP diagnosis is a very important part of an adequate and prompt treatment, and the search of pre-symptomatic biomarkers is vital. The whole saliva is a reliable diagnostic fluid which is being used in some diseases, because itās easier to obtain and analyze than blood, and it has some proteins in common with serum, which were filtered from it. The salivary glands of FAP individuals contain TTR deposits that can influence the proteome and post-translational modifications, such as glycation, that can be used as biomarkers. In the present work we were able to observe distinct electrophoretic profiles in the saliva of FAP patients. We also identified new proteins in saliva, such as Ī±-synuclein, which also presented an altered electrophoretic profile. The identified proteins were mostly from serum. On the other hand, it was observed a differential expression of FAP proteins, some of those with glycated residues. Mean while, it was observed an higher percentage of TTR monomers than tetramers in FAP saliva. The identification of differentially expressed saliva proteins in FAP individuals, was accomplished, and these FAP biomarkers can be considered as pre-symptomatic biomarkers.
DescriĆ§Ć£o
Tese de mestrado, BioquĆmica (BioquĆmica MĆ©dica), Universidade de Lisboa, Faculdade de CiĆŖncias, 2010
Palavras-chave
PAF TTR Biomarcadores Saliva GlicaĆ§Ć£o Teses de mestrado - 2010