| Abstract [eng] |
Amyloidogenic protein aggregation is linked with the onset and progression of multiple amyloidoses, including neurodegenerative Alzheimer‘s and Parkinson‘s diseases. Despite decades of intense research and countless experiments, there are still very few effective, disease-modifying drugs or treatments available. Coupled with the fact that the number of amyloid-related diseases is projected to further increase, this makes it vitally important to obtain a better understanding of the amyloid aggregation process, as well as search for potential anti-amyloid compounds. In this work, the interaction between amyloidophilic molecules and protein amyloid fibrils was investigated using multiple approaches. First part of the study was dedicated towards understanding the relationship between environmental conditions and the resulting fibril types, as well as their affinity towards an aggregate-specific dye – thioflavin-T. The second part of the study was dedicated towards understanding how different amyloidophilic molecules interact with protein aggregates. It was observed that there are multiple possible binding modes for such compounds, including ones not related to the surface of the amyloid fibril. Using the knowledge obtained during these studies, it was investigated whether lysozyme amyloid fibrils could be used as a means of selectively separating anti-amyloid compounds from multiple complex mixtures. Analyzing the bound and non-bound compounds separately revealed that all molecules, which possess anti-amyloid properties, became bound to the lysozyme aggregates. These compounds could later be separated from the fibrils using three distinct methods and they were capable of inhibiting amyloid aggregation. |
