Efeito de compostos fenólicos e probióticos em modelo parkinsoniano de Saccharomyces cerevisiae

Abstract

Parkinson's disease (PD) is a progressive neurodegenerative disorder associated mainly with aging and that has not been cured until now. The current understanding of the pathophysiology of PD suggests a central role in the accumulation of the protein α-synuclein (α -sin) and several evidences have been directing that the initial site of this process would be the enteric nervous system. It is known that the intake of phenolic substances contributes to the redox balance of the organism, however its bioactivities are highly impacted by microbial biotransformations that occur in the intestinal lumen. The objective of this work was to evaluate the influence of microbial biotransformations on the antioxidant activity of phenolic substances phenethyl ester of caffeic acid (CAPE) and mangiferin, as well as their effects on the toxicity of α-synuclein protein, both in eukaryotic cells of the yeast Saccharomyces cerevisiae. In the tests to evaluate the antioxidant activity, CAPE and mangiferin (0.1 mM) decreased the oxidative damage induced by hydrogen peroxide in the control strain (BY4741) and in the mutant strains sod1, gsh1 and ctt1, deficient in antioxidant systems. Microbial fermentation maintained the antioxidant capacity of CAPE and mangiferin in the in vivo model, revealing an increase only with CAPE in the in vitro analysis. However, this mangiferin activity was not significant in intracellular viability and oxidation tests. When the CAPE and mangiferin substances were evaluated in transformed yeast that expressed the α-synuclein gene, it was observed that the substances without fermentation did not inhibit the aggregation of the protein, but that their fermentates reduced the aggregation by about 50% in the fluorescence microscopy assay. The inhibition of aggregation was not correlated with antioxidant activity, but with the presence of fermented metabolites. The detection of 3-HPPA, a microbial metabolite associated with the reduction of α-sin toxicity, converges with recent theories that the microbiota influences the etiology of Parkinson's disease, however further studies are needed to investigate which microorganisms would produce this metabolite and whether other products of microbial metabolism are involved in reducing the toxicity of α-sin. The results of our studies suggest that interactions between the microbiome and certain dietary factors may support new therapeutic strategies to modulate the onset and/or progression of synucleinopathies.