| Abstract [eng] |
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease related amyloid aggregation of misfolded molecules of superoxide dismutase-1 (SOD1), leading to accumulation of insoluble neurofibrilar tangles in motor neurons. Currently, there is no medicine that could fully cure ALS, altgough scientists are actively searching for coumpounds that would inhibit amyloid aggregation of SOD1. There is a hypothesis that other amyloid proteins could affect SOD1 aggregation as well, because there are known cases of neurofibrilar clusters composed of molecules of different proteins. During this work the effect of 64 sulfonamides on SOD1 aggregation was examined and it was shown that SOD1 aggregation is most inhibited when the compound AV20-07-2 is being used while E69 stimulates the aggregation process the most. There was also shown that alpha-synuclein (ASyn), a protein involved in Parkinson’s disease pathology, act as a SOD1 aggregation accelerator. However, when ASyn monomers were added to SOD1 solution, AV20-07-2 lost its capability of inhibiting SOD1 aggregation although the aggregation inhibitory effect was maintained when ASyn aggregates were used. FTIR spectra of formed aggregates showed no significant difference in the secondary structures between SOD1 fibrils while the change of absorption values might be caused by unequal quantity of ASyn aggregates in the samples. |
