| Abstract [eng] |
The aggregation of amyloid proteins into fibrils is associated with various neurodegenerative diseases, such as Alzheimer's, Parkinson's and prion diseases. Despite many years of research in this field, many unanswered questions remain about the specifics of fibril formation. In this work was investigated how environmental factors—such as temperature, pH, ionic strength, and protein-protein interactions—influence the amyloid aggregation of several key proteins, including lysozyme, insulin, alpha-synuclein and prion protein. The research addressed the phenomenon of fibril polymorphism, where the same protein can form structurally and morphologically distinct aggregates under varying or even identical conditions. A major focus of the work was dedicated to investigate the relationship between a protein's initial folding state and the resulting fibril structure. Using lysozyme as a model, the study demonstrated that protein unfolding, driven by temperature and pH, significantly promoted structural variability and the formation of distinct fibril types. The other part of this study also examined the sensitivity of insulin aggregation to minor changes in its chemical environment, finding that its secondary structure and morphology were highly dependent on the specific solution components. Finally, the last part of research highlighted the complexity of the "amyloid interactome" by demonstrating that cross-interactions with proteins like SOD1 and S100A9 can inhibit the nucleation of prion proteins and stabilize specific, single-aggregate strains. |
