Yeast Saccharomyces cerevisiae play an important role as a model organism for understanding the development of various neurodegenerative diseases. Their ease of cultivation and sufficient resemblance to mammalian cells have contributed to their general use in various scientific studies. Neurodegenerative diseases are a problem and a challenge of modern times, as they are the result of an aging population and the extended expectancy of human life. Amyotrophic lateral sclerosis (ALS) is a rare neurodegenerative disease. It affects motor neurons in the brain and spinal cord and causes their degeneration with cytoplasmic aggregates of the TDP-43 protein. The aim of the thesis was to study the yeast response to the presence of cytotoxic aggregates of protein TDP-43-GFP. Yeast were grown in successive batch cultivations and were observed using a fluorescence microscope at different stages of growth. At the same time, fluorescence intensity was measured to indicate the expression of the inserted human TDP-43-GFP gene, biomass yield for the effect of aggregates on cell growth and reproduction, and cellular metabolic activity as a reflection of energy needs for cellular stress response to the presence of aggregates. Experiments have revealed the stress effect of aggregates on cells and their response. Interestingly, the culture initially cultured in expression and then in the repression medium and yet again re-cultured in the expression medium was better prepared for aggregation stress after 8 hours of cultivation, which was reflected in lower gene expression intensity, higher biomass yield, and increased initial cellular metabolism. Our results could significantly help to understand the development of ALS in the formation and removal of TDP-43 protein aggregates.
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