I. Um novo olhar para as ureases : propriedades neurotóxicas e possível envolvimento em doenças neurodegenerativas. II. Análises de reposicionamento de drogas no combate a Covid19

Abstract

(Artigo : Um novo olhar para as urease: Propriedades neurotóxicas e possível envolvimento em doenças 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).