| Abstract [eng] |
lzheimer's disease is the most common form of dementia. The hallmarks of Alzheimer disease (AD) include aggregation and accumulation of Aβ peptide and S100A9 protein in the brain. Different types of aggregates (oligomers, amyloid fibrils and amorphous aggregates) can interact with plasma membrane and cause it damage. The main objective of this work was to investigate the effect of S100A9 protein and Aβ peptide on model plasma membrane systems. During this work recombinant S100A9 protein was purified. The size of S100A9 aggregates formed under different conditions was estimated by using dynamic light scattering (DLS). It was found that after incubation of proteins at different temperatures of 22 °C, 37 °C and 60 °C, oligomers, short protofilaments, and fibrils were formed, respectively. To investigate the damage caused by these structures to the membrane, tethered bilayer lipid membranes (tBLM) were used. By employing electrochemical impedance spectroscopy, changes in the electrical properties of the membrane were observed. Atomic force microscopy (AFM) was used to determine the morphology of structures formed by the Aβ1-42 peptide. The ability of Aβ1-42 oligomers and fibrils to disrupt the lipid bilayer integrity was observed by changes in the fluorescence intensity of the calcein incorporated into the liposomes. Results have shown that the level of membrane damage caused by S100A9 protein and Aβ1-42 peptide depends on the size of their aggregates. Oligomeric species are more toxic to the membrane compared to fibrils and monomers. |
