I. Um novo olhar para as ureases : propriedades neurot?xicas e poss?vel envolvimento em doen?as neurodegenerativas. II. An?lises de reposicionamento de drogas no combate a Covid19
Ano de defesa: | 2023 |
---|---|
Autor(a) principal: | |
Orientador(a): | |
Banca de defesa: | |
Tipo de documento: | Tese |
Tipo de acesso: | Acesso aberto |
Idioma: | por |
Instituição de defesa: |
Pontif?cia Universidade Cat?lica do Rio Grande do Sul
|
Programa de Pós-Graduação: |
Programa de P?s-Gradua??o em Medicina e Ci?ncias da Sa?de
|
Departamento: |
Escola de Medicina
|
País: |
Brasil
|
Palavras-chave em Português: | |
Palavras-chave em Inglês: | |
Área do conhecimento CNPq: | |
Link de acesso: | https://tede2.pucrs.br/tede2/handle/tede/10689 |
Resumo: | (Artigo : Um novo olhar para as urease: Propriedades neurot?xicas e poss?vel envolvimento em doen?as neurodegenerativas). Proteus mirabilis is the main representative bacterium of the genus Proteus, of the order Enterobacteriacea. With the form of a gram-negative rod, being facultative anaerobic, heterotrophic and urease producer, this microorganism is part of the intestinal microbiota of several animals. P. mirabilis accounts for 80-90% of all infections caused by Proteus sp. in humans, which can be of several types, including urinary, ocular, ophthalmic, and respiratory. Urinary infections caused by this pathogen are facilitated by the production of ammonia due to the ureolytic action of urease, which is produced by the bacteria. The elevation of local pH, caused by ammonia, allows the precipitation of salts that form kidney stones, which are colonized by bacteria, facilitating their proliferation and permanence. Ureases share about 60% of their amino acid sequence and can be produced by plants, fungi and bacteria, however they are not synthesized by animals. These proteins promote effects independent of their enzymatic activity, first described for ureases from Canavalia ensiformis (jack bean, JBU) and canatoxin (CNTX). Among the biological effects are the lethal neurotoxic activity for rats and mice. In addition, they induce exocytosis in mammalian cells, pro-inflammatory effect, antifungal and entomotoxic activities. The literature reports behavioral studies demonstrating that, after oral administration of P. mirabilis, mice developed biochemical alterations and motor deficits similar to Parkinson's disease. Another bacterium that produces large amounts of urease, the gastric pathogen Helicobacter pylori, has been linked to Alzheimer's disease. H. pylori urease, in addition to helping colonize the stomach through alkalinization of the medium, also has non-enzymatic biological properties described for other ureases, causing exocytosis, platelet aggregation and proinflammatory effects, as well as angiogenic activity. In view of the various biological effects of ureases and their importance for the clinical manifestations of P. mirabilis and H. pylori, this project aimed to characterize the neurotoxic and pro-inflammatory effects triggered mainly by P. mirabilis urease, and also of H. pylori urease, and to investigate the possible involvement of ureases with neurodegenerative diseases caused by each pathogen (P. mirabilis, Parkinson's disease and H. pylori, Alzheimer's disease). |
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Costa, Jaderson Costa dahttp://lattes.cnpq.br/9962204158580009Grahl, Matheus Vin?cius Coste2023-03-30T18:04:20Z2023-01-30https://tede2.pucrs.br/tede2/handle/tede/10689(Artigo : Um novo olhar para as urease: Propriedades neurot?xicas e poss?vel envolvimento em doen?as neurodegenerativas). Proteus mirabilis is the main representative bacterium of the genus Proteus, of the order Enterobacteriacea. With the form of a gram-negative rod, being facultative anaerobic, heterotrophic and urease producer, this microorganism is part of the intestinal microbiota of several animals. P. mirabilis accounts for 80-90% of all infections caused by Proteus sp. in humans, which can be of several types, including urinary, ocular, ophthalmic, and respiratory. Urinary infections caused by this pathogen are facilitated by the production of ammonia due to the ureolytic action of urease, which is produced by the bacteria. The elevation of local pH, caused by ammonia, allows the precipitation of salts that form kidney stones, which are colonized by bacteria, facilitating their proliferation and permanence. Ureases share about 60% of their amino acid sequence and can be produced by plants, fungi and bacteria, however they are not synthesized by animals. These proteins promote effects independent of their enzymatic activity, first described for ureases from Canavalia ensiformis (jack bean, JBU) and canatoxin (CNTX). Among the biological effects are the lethal neurotoxic activity for rats and mice. In addition, they induce exocytosis in mammalian cells, pro-inflammatory effect, antifungal and entomotoxic activities. The literature reports behavioral studies demonstrating that, after oral administration of P. mirabilis, mice developed biochemical alterations and motor deficits similar to Parkinson's disease. Another bacterium that produces large amounts of urease, the gastric pathogen Helicobacter pylori, has been linked to Alzheimer's disease. H. pylori urease, in addition to helping colonize the stomach through alkalinization of the medium, also has non-enzymatic biological properties described for other ureases, causing exocytosis, platelet aggregation and proinflammatory effects, as well as angiogenic activity. In view of the various biological effects of ureases and their importance for the clinical manifestations of P. mirabilis and H. pylori, this project aimed to characterize the neurotoxic and pro-inflammatory effects triggered mainly by P. mirabilis urease, and also of H. pylori urease, and to investigate the possible involvement of ureases with neurodegenerative diseases caused by each pathogen (P. mirabilis, Parkinson's disease and H. pylori, Alzheimer's disease).(Artigo : Um novo olhar para as urease: Propriedades neurot?xicas e poss?vel envolvimento em doen?as neurodegenerativas). Proteus mirabilis ? a principal bact?ria representante do g?nero Proteus, da ordem Enterobacteriacea. Com forma de bastonete gram-negativo, sendo anaer?bia facultativa, heterotr?fica e produtora de urease, este microganismo faz parte da microbiota intestinal de diversos animais. P. mirabilis representa 80-90% de todos os casos de infec??es causadas por Proteus sp. em humanos, que podem ser de diversos tipos, incluindo urin?rias, oculares, oftalmol?gicas e respirat?rias. As infec??es urin?rias causadas por esse pat?geno s?o facilitadas pela produ??o de am?nia devido a a??o ureol?tica da urease, que ? produzida pela bact?ria. A eleva??o do pH local, ocasionada pela am?nia, permite a precipita??o de sais que formam os c?lculos renais, os quais s?o colonizados pela bact?ria, facilitando sua prolifera??o e perman?ncia. As ureases compartilham cerca de 60% da sua sequ?ncia de amino?cidos e podem ser produzidas por plantas, fungos e bact?rias, no entanto n?o s?o sintetizadas por animais. Estas prote?nas promovem efeitos independentes de sua atividade enzim?tica, descritos primeiramente para as ureases de Canavalia ensiformis (jack bean, JBU) e canatoxina (CNTX). Dentre os efeitos biol?gicos est?o a atividade neurot?xica letal para ratos e camundongos. Al?m disso, induzem exocitose em c?lulas de mam?feros, efeito pr?-inflamat?rio, atividade antif?ngica e entomot?xica. A literatura relata estudos comportamentais demonstrando que, ap?s a administra??o oral de P. mirabilis, os camundongos desenvolveram altera??es bioqu?micas e deficit motores semelhantes a doen?a de Parkinson. Outra bact?ria que produz grande quantidade de urease, o pat?geno g?strico Helicobacter pylori, tem sido associado ? Doen?a de Alzheimer. A urease de H. pylori, al?m de auxiliar na coloniza??o do est?mago atrav?s da alcaliniza??o do meio, tamb?m apresenta propriedades biol?gicas n?o enzim?ticas descritas para as outras ureases, causando exocitose, agrega??o plaquet?ria e efeitos pr?-inflamat?rios, bem como atividade angiog?nica. Tendo em vista os diversos efeitos biol?gicos das ureases e a import?ncia dela para as manifesta??es cl?nicas de P. mirabilis e H. pylori, este projeto teve como objetivo caracterizar os efeitos neurot?xicos e pro-inflamat?rios desencadeados primeiramente pela urease de P. mirabilis e tamb?m da urease de H. pylori, e averiguar o poss?vel envolvimento das ureases com doen?as neurodegenerativas ocasionadas por cada pat?geno (P. mirabilis, doen?a de Parkinson e H. pylori, doen?a de Alzheimer).Submitted by PPG Medicina e Ci?ncias da Sa?de (medicina-pg@pucrs.br) on 2023-03-28T18:03:42Z No. of bitstreams: 1 Matheus Vinicius Coste Grahl - Tese p?s banca_compressed (1).pdf: 5980036 bytes, checksum: 683f0c0375815dff00efd26869c35729 (MD5)Approved for entry into archive by Sheila Dias (sheila.dias@pucrs.br) on 2023-03-30T17:17:15Z (GMT) No. of bitstreams: 1 Matheus Vinicius Coste Grahl - Tese p?s banca_compressed (1).pdf: 5980036 bytes, checksum: 683f0c0375815dff00efd26869c35729 (MD5)Made available in DSpace on 2023-03-30T18:04:20Z (GMT). No. of bitstreams: 1 Matheus Vinicius Coste Grahl - Tese p?s banca_compressed (1).pdf: 5980036 bytes, checksum: 683f0c0375815dff00efd26869c35729 (MD5) Previous issue date: 2023-01-30Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPESapplication/pdfhttps://tede2.pucrs.br/tede2/retrieve/186925/TES_MATHEUS_VINICIUS_COSTE_GRAHL_CONFIDENCIAL.pdf.jpgporPontif?cia Universidade Cat?lica do Rio Grande do SulPrograma de P?s-Gradua??o em Medicina e Ci?ncias da Sa?dePUCRSBrasilEscola de MedicinaDoen?a de ParkinsonNeurotoxinasUreaseSARS-CoV-2COVID19Parkinson's DiseaseNeurotoxinsUreaseSARS-CoV-2COVID19CIENCIAS DA SAUDE::MEDICINAI. Um novo olhar para as ureases : propriedades neurot?xicas e poss?vel envolvimento em doen?as neurodegenerativas. II. 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dc.title.por.fl_str_mv |
I. Um novo olhar para as ureases : propriedades neurot?xicas e poss?vel envolvimento em doen?as neurodegenerativas. II. An?lises de reposicionamento de drogas no combate a Covid19 |
title |
I. Um novo olhar para as ureases : propriedades neurot?xicas e poss?vel envolvimento em doen?as neurodegenerativas. II. An?lises de reposicionamento de drogas no combate a Covid19 |
spellingShingle |
I. Um novo olhar para as ureases : propriedades neurot?xicas e poss?vel envolvimento em doen?as neurodegenerativas. II. An?lises de reposicionamento de drogas no combate a Covid19 Grahl, Matheus Vin?cius Coste Doen?a de Parkinson Neurotoxinas Urease SARS-CoV-2 COVID19 Parkinson's Disease Neurotoxins Urease SARS-CoV-2 COVID19 CIENCIAS DA SAUDE::MEDICINA |
title_short |
I. Um novo olhar para as ureases : propriedades neurot?xicas e poss?vel envolvimento em doen?as neurodegenerativas. II. An?lises de reposicionamento de drogas no combate a Covid19 |
title_full |
I. Um novo olhar para as ureases : propriedades neurot?xicas e poss?vel envolvimento em doen?as neurodegenerativas. II. An?lises de reposicionamento de drogas no combate a Covid19 |
title_fullStr |
I. Um novo olhar para as ureases : propriedades neurot?xicas e poss?vel envolvimento em doen?as neurodegenerativas. II. An?lises de reposicionamento de drogas no combate a Covid19 |
title_full_unstemmed |
I. Um novo olhar para as ureases : propriedades neurot?xicas e poss?vel envolvimento em doen?as neurodegenerativas. II. An?lises de reposicionamento de drogas no combate a Covid19 |
title_sort |
I. Um novo olhar para as ureases : propriedades neurot?xicas e poss?vel envolvimento em doen?as neurodegenerativas. II. An?lises de reposicionamento de drogas no combate a Covid19 |
author |
Grahl, Matheus Vin?cius Coste |
author_facet |
Grahl, Matheus Vin?cius Coste |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Costa, Jaderson Costa da |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/9962204158580009 |
dc.contributor.author.fl_str_mv |
Grahl, Matheus Vin?cius Coste |
contributor_str_mv |
Costa, Jaderson Costa da |
dc.subject.por.fl_str_mv |
Doen?a de Parkinson Neurotoxinas Urease SARS-CoV-2 COVID19 |
topic |
Doen?a de Parkinson Neurotoxinas Urease SARS-CoV-2 COVID19 Parkinson's Disease Neurotoxins Urease SARS-CoV-2 COVID19 CIENCIAS DA SAUDE::MEDICINA |
dc.subject.eng.fl_str_mv |
Parkinson's Disease Neurotoxins Urease SARS-CoV-2 COVID19 |
dc.subject.cnpq.fl_str_mv |
CIENCIAS DA SAUDE::MEDICINA |
description |
(Artigo : Um novo olhar para as urease: Propriedades neurot?xicas e poss?vel envolvimento em doen?as neurodegenerativas). Proteus mirabilis is the main representative bacterium of the genus Proteus, of the order Enterobacteriacea. With the form of a gram-negative rod, being facultative anaerobic, heterotrophic and urease producer, this microorganism is part of the intestinal microbiota of several animals. P. mirabilis accounts for 80-90% of all infections caused by Proteus sp. in humans, which can be of several types, including urinary, ocular, ophthalmic, and respiratory. Urinary infections caused by this pathogen are facilitated by the production of ammonia due to the ureolytic action of urease, which is produced by the bacteria. The elevation of local pH, caused by ammonia, allows the precipitation of salts that form kidney stones, which are colonized by bacteria, facilitating their proliferation and permanence. Ureases share about 60% of their amino acid sequence and can be produced by plants, fungi and bacteria, however they are not synthesized by animals. These proteins promote effects independent of their enzymatic activity, first described for ureases from Canavalia ensiformis (jack bean, JBU) and canatoxin (CNTX). Among the biological effects are the lethal neurotoxic activity for rats and mice. In addition, they induce exocytosis in mammalian cells, pro-inflammatory effect, antifungal and entomotoxic activities. The literature reports behavioral studies demonstrating that, after oral administration of P. mirabilis, mice developed biochemical alterations and motor deficits similar to Parkinson's disease. Another bacterium that produces large amounts of urease, the gastric pathogen Helicobacter pylori, has been linked to Alzheimer's disease. H. pylori urease, in addition to helping colonize the stomach through alkalinization of the medium, also has non-enzymatic biological properties described for other ureases, causing exocytosis, platelet aggregation and proinflammatory effects, as well as angiogenic activity. In view of the various biological effects of ureases and their importance for the clinical manifestations of P. mirabilis and H. pylori, this project aimed to characterize the neurotoxic and pro-inflammatory effects triggered mainly by P. mirabilis urease, and also of H. pylori urease, and to investigate the possible involvement of ureases with neurodegenerative diseases caused by each pathogen (P. mirabilis, Parkinson's disease and H. pylori, Alzheimer's disease). |
publishDate |
2023 |
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2023-03-30T18:04:20Z |
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2023-01-30 |
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