Study of the inhibitory effect of the small molecule Diethylthia tri carbocyanine iodide, as an anti- Alzheimer's candidate drug on human recombinant tau aggregation

摘要

Background and aims: Alzheimer’s disease is a neurodegenerative disorder that is affected by different factors. Forming aggregations of the tau proteins in the brain is one of the most commonly observation in the patients’ brains suffered from this disease. Several strategies have been devised to target the tau aggregates in the neuronal cells of the patients. Recently, chaperones have drawn the attention of the researchers as a tool to inhibit or disaggregate the tau protein aggregations. The aim of this study was to investigate the effect of small molecule chaperone called Diethylthia tri carbocyanine iodide on the formation of tau aggregates. Methods: In this basic laboratory study, Tau protein was expressed in bacteria. Then, Tau protein was purified by the ion-exchange chromatography and affinity chromatography, and its purity was evaluated by SDS-PAGE. Heparin was added as the inducer of tau aggregation, and the inductive effect of heparin on tau aggregation was examinated by circular dichroism (CD) method. Then, Diethylthia tri carbocyanine iodide chaperones was added to the aggregated tau and its effect was evaluated using SDS-PAGE and thioflavin T fluorescence assay. Results: Electrophoresis SDS-PAGE confirmed the expression of tau protein and its purity. CD validated the successful induction of tau aggregation by heparin. Following treatment of the tau aggregates with Diethylthia tri carbocyanine iodide, the results of SDS-PAGE showed that induced aggregation, remarkably reduced compared to the control sample. Thioflavin T fluorescence assay was used to confirm the results of SDS-PAGE analysis. Conclusion: The results of this study showed that Diethylthia tri carbocyanine iodide could inhibit the aggregation of the tau protein which they were produced in the presence of heparin inductor. These results can propose Diethylthia tri carbocyanine iodide as a potential treatment to target the tau aggregates in people with Alzheimer’s disease.