| Abstract [eng] |
The protein aggregation process between proteins of different nature can be influenced by their interactions. Coaggregation between disease-associated protein Aβ and cellular PrP has a key role in Alzheimer's disease. Although the coaggregation process of these proteins is slower compared with a single Aβ, the resulting aggregates are cytotoxic. Amyloid inhibitors can act to stabilize the protein structure, inhibit amyloid fibril elongation processes, or reduce cellular toxicity. The aim of this work was to perform the aggregation of mouse prion protein mutants (MoPrP23-143 and MoPrP89-230) and Aβ42. Then the influence of flavones (and its oxidized forms) to aggregation process was evaluated as well as Aβ+MoPrP+flavones toxicity to cells. First, aggregation of MoPrP mutants and Aβ was performed by recording the change in ThT fluorescence intensity values over time. It was found that both MoPrP23-143 and MoPrP89-230 inhibit aggregation process of amyloid-β. Analysis of cell viability showed that aggregates formed in the cellular environment were more toxic than final phase amyloid fibrils. To determine the interaction between Aβ and MoPrP mutants, the morphology assay was performed by using AFM. The assay revealed that coaggregation of Aβ+MoPrP23-143 occurs upon aggregation of both proteins. In the case of Aβ+MoPrP89-230, only Aβ42 aggregates into amyloid fibrils. The influence of oxidized and non-oxidized flavones on the amyloid coaggregation process was evaluated by aggregation halftimes (by tracking the ThT fluorescence intensity values). The results indicated that small part of the oxidized/non-oxidized flavones inhibited the aggregation process of Aβ+MoPrP mutants as well as increased cell viability. |
