| Abstract [eng] |
Alzheimer’s and Parkinson’s diseases are the most common forms of neurodegeneration. Despite the difference in cognitive symptoms, affected regions in the brain and the rate of disease progression, their pathophysiological hallmark is similar and considered to be linked with protein aggregation into insoluble particles that accumulate in the cerebrum. The projected steady increase in future patients has led to various drug research and clinical trials. However, the success rate of these trials showcases the need for further studies to deepen the knowledge about the potential drugs and improve drug research methods. In this thesis, polyphenolic nature molecules (epigallocatechin-3-gallate (EGCG), gallic acid and various hydroxyflavones) were investigated to understand their inhibitory potential against protein aggregation. While the portion of these molecules autoxidize at neutral or higher pH, the investigation was done with the initial and autoxidized forms. It was evident that autoxidation is a crucial process enabling their inhibitory potential against protein aggregation. In addition to that, during the study with a large number of flavones, the relationship between the structure of flavone, its autoxidation and aggregation inhibition was established. Another part of this thesis was dedicated to understanding whether cerebrospinal fluid components are critical during the in vitro anti-amyloid molecules screening procedure. Analyzing the inhibition of amyloid-beta aggregation in the reaction mixture with major CSF components showed the pronounced effect of these components not only on the inhibitory potential of benzenesulfonamide VR16-09 and oxidized EGCG but also on the amyloid beta aggregation. |
