Įvairių aplinkos veiksnių įtaka S100A9 baltymo agregacijai / ; The impact of various environmental factors on the aggregation of s100a9 protein.

The Impact of Various Environmental Factors on the Aggregation of S100A9 Protein S100A9 belongs to the S100 protein family, which expresses a plethora of intracellular and extracellular functions. Recently, S100A9 has emerged as a potential contributor to Alzheimer‘s disease, alongside with amyloid beta and tau protein. S100A9 was shown to be able to form amyloid fibrils in vivo and in vitro. The aim of this thesis is to analyse how environmetal factors influence the aggregation of S100A9 protein. Understanding factors contributing to this phenomenon could help tackle the problem of aggregation. This thesis is focused on the differences in aggregation of S100A9 given the changes in temperature and the addition of GuHCl, ethanol and low concentrations of Ca2+. The major part of this thesis was spent searching for potential inhibitors as there are currently no scientific articles regarding this matter. The results show that increasing temperature, small quantities of GuHCl or the addition of ethanol promotes the aggregation of S100A9. It was also confirmed that excess calcium inhibits the formation of amyloid fibrils, whereas lower Ca2+ concentrations did not have any significant impact on this process. A total number of 155 flavonoids were tested and 47 out of them were able to slow down aggregation with quercetin exhibiting the strongest inhibitory effect. Unfortunately, well known inhibitors – EGCG and resveratrol - had no effect on the aggregation of this protein.