Yeast red pigment, protein aggregates, and amyloidoses: a review.

Estimating the amyloid level in yeast Saccharomyces, we found out that the red pigment (product of polymerization of aminoimidazole ribotide) accumulating in ade1 and ade2 mutants leads to drop of the amyloid content. We demonstrated in vitro that fibrils of several proteins grown in the presence of the red pigment stop formation at the protofibril stage and form stable aggregates due to coalescence. Also, the red pigment inhibits reactive oxygen species accumulation in cells. This observation suggests that red pigment is involved in oxidative stress response. We developed an approach to identify the proteins whose aggregation state depends on prion (amyloid) or red pigment presence. These sets of proteins overlap and in both cases involve many different chaperones. Red pigment binds amyloids and is supposed to prevent chaperone-mediated prion propagation. An original yeast-Drosophila model was offered to estimate the red pigment effect on human proteins involved in neurodegeneration. As yeast cells are a natural feed of Drosophila, we could compare the data on transgenic flies fed on red and white yeast cells. Red pigment inhibits aggregation of human Amyloid beta and α-synuclein expressed in yeast cells. In the brain of transgenic flies, the red pigment diminishes amyloid beta level and the area of neurodegeneration. An improvement in memory and viability accompanied these changes. In transgenic flies expressing human α-synuclein, the pigment leads to a decreased death rate of dopaminergic neurons and improves mobility. The obtained results demonstrate yeast red pigment potential for the treatment of neurodegenerative diseases.

Yeast red pigment modifies Amyloid beta growth in Alzheimer disease models in both Saccharomyces cerevisiae and Drosophila melanogaster.

The effect of yeast red pigment on amyloid-ß (Aß) aggregation and fibril growth was studied in yeasts, fruit flies and in vitro. Yeast strains accumulating red pigment (red strains) contained less amyloid and had better survival rates compared to isogenic strains without red pigment accumulation (white strains). Confocal and fluorescent microscopy was used to visualise fluorescent Aß-GFP aggregates. Yeast cells containing less red pigment had more Aß-GFP aggregates despite the lower level of overall GFP fluorescence. Western blot analysis with anti-GFP, anti-Aß and A11 antibodies also revealed that red cells contained a considerably lower amount of Aß GFP aggregates as compared to white cells. Similar results were obtained with exogenous red pigment that was able to penetrate yeast cells. In vitro experiments with thioflavine and TEM showed that red pigment effectively decreased Aß fibril growth. Transgenic flies expressing Aß were cultivated on medium containing red and white isogenic yeast strains. Flies cultivated on red strains had a significant decrease in Aß accumulation levels and brain neurodegeneration. They also demonstrated better memory and learning indexes and higher locomotor ability.