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Authors
Abstract(s)
A cárie dentária é a doença infeciosa crónica mais prevalente no mundo,
sendo que uma grande parte da população não se encontra tratada. Esta doença
provoca crises dolorosas que requerem tratamentos dispendiosos que nem
sempre estão disponíveis, principalmente em lesões extensas que envolvam a
dentina. A diminuição acentuada na qualidade de vida destas pessoas, leva à
necessidade de compreensão dos processos patológicos envolvidos no
estabelecimento da cárie dentária e desenvolvimento de novas estratégias de
diagnóstico e terapêutica. Assim, com este estudo, teve-se o objetivo de
conhecer os mecanismos moleculares envolvidos em cárie, identificar potenciais
biomarcadores e verificar os eventos de interação entre as moléculas do
hospedeiro e do microbiota envolvente.
A catalogação das proteínas salivares em cárie dentária, permitiu a adição
de 6107 novas proteínas às 179 anteriormente anotadas. A caracterização
funcional do OralOma de cárie, comparada com o OralOma normal, permitiu
inferir um aumento do número de proteínas envolvidas nos processos
moleculares enzyme regulator activity, antioxidant activity e structural molecule
activity. As proteínas envolvidas no processo enzyme regulator activity estão
fortemente associadas à regulação das Metalo Proteinases da Matriz (MMPs). A
análise interatómica permitiu verificar que um grande número de interações está
associado a funções de defesa e à tentativa de invasão e colonização dos
tecidos do hospedeiro.
O facto das proteínas catalogadas não apresentarem dados de
quantificação limita a identificação de potenciais biomarcadores para a cárie
dentária. Sugerem-se então, novos estudos de proteómica, que permitam esta
quantificação. Ao longo deste trabalho, verificou-se também, que a maioria dos
estudos referentes à cárie dentária se restringe ao esmalte, no entanto, este
processo deve ser melhor clarificado em relação à dentina. Este estudo in silico
demonstra que uma grande parte das proteínas envolvidas, estão associadas à
regulação das MMPs, sendo, portanto, proposto que devam ser estudadas como
alvo terapêutico na prevenção da cárie. Conclui-se que é necessário definir
novas estratégias terapêuticas baseadas no conhecimento molecular.
Dental caries is the most prevalent chronic infectious disease worldwide, and a majority of the population remains untreated. This disease can cause painful crises and requires costly treatments that not always available, especially in extensive lesions involving dentin. The fast decrease in people's quality of life leads to the need of understanding the pathological processes involved in the establishment of the dental caries and the development of new strategies of diagnosis and therapy. Therefore, with this study, the goal was to know the molecular mechanisms involved in the dental caries, identify potential biomarkers and verify the interaction events between host molecules and the surrounding microbiota. Cataloging salivary proteins in the dental caries has allowed to add 6107 new proteins to the 179 previously annotated. The functional characterization of the dental caries OralOme, compared to the normal OralOme, has showed an increase on the number of proteins involved in the molecular process of enzyme regulator activity, antioxidant activity and structural molecule activity. The proteins involved in the enzyme regulator activity process are strongly associated to the MMPs regulation. The interactomics analysis showed that a large number of interactions is associated to the defense and to the attempt of invasion and colonization of the host tissues. The fact that catalogued proteins don't present quantification data, limits the identification of potential biomarkers for dental caries. New proteomics studies are suggested, to provide this quantification. Through this work, it was, also, verified that the majority of dental caries related studies are restricted to the dental enamel, however, this process has to be better clarified when it comes to the dentine. This in silico study demonstrates that a large part of the proteins involved are associated to MMPs regulation, suggesting, that these may be studied as a therapeutic target in the dental caries prevention. It is concluded that it is necessary to define new therapeutic strategies based on molecular knowledge.
Dental caries is the most prevalent chronic infectious disease worldwide, and a majority of the population remains untreated. This disease can cause painful crises and requires costly treatments that not always available, especially in extensive lesions involving dentin. The fast decrease in people's quality of life leads to the need of understanding the pathological processes involved in the establishment of the dental caries and the development of new strategies of diagnosis and therapy. Therefore, with this study, the goal was to know the molecular mechanisms involved in the dental caries, identify potential biomarkers and verify the interaction events between host molecules and the surrounding microbiota. Cataloging salivary proteins in the dental caries has allowed to add 6107 new proteins to the 179 previously annotated. The functional characterization of the dental caries OralOme, compared to the normal OralOme, has showed an increase on the number of proteins involved in the molecular process of enzyme regulator activity, antioxidant activity and structural molecule activity. The proteins involved in the enzyme regulator activity process are strongly associated to the MMPs regulation. The interactomics analysis showed that a large number of interactions is associated to the defense and to the attempt of invasion and colonization of the host tissues. The fact that catalogued proteins don't present quantification data, limits the identification of potential biomarkers for dental caries. New proteomics studies are suggested, to provide this quantification. Through this work, it was, also, verified that the majority of dental caries related studies are restricted to the dental enamel, however, this process has to be better clarified when it comes to the dentine. This in silico study demonstrates that a large part of the proteins involved are associated to MMPs regulation, suggesting, that these may be studied as a therapeutic target in the dental caries prevention. It is concluded that it is necessary to define new therapeutic strategies based on molecular knowledge.
Description
Keywords
Cárie dentária Biomarcadores Proteómica Proteínas Dental caries Biomarkers Proteomic Proteins