Multi-approach study of tripeptides to depolymerize amyloid beta fibrils
2015
Polish Academy of Sciences, Warsaw, Poland(1)
Slovak Academy of Sciences, Košice, Slovakia(2)
Slovak Academy of Sciences, Košice, Slovakia(2)
The aggregation of amyloid-beta and the formation of fibrils has been proposed as the main cause driving Alzheimer's disease pathology. Despite the lack of effective treatments, there is experimental data that suggests that the reversion of amyloid aggregation can reduce the symptoms of the disease. In this study, all the tripeptides were screened for their amyloid beta depolymerization capabilities. Different computational approaches revealed four tripeptides with high binding affinity to amyloid aggregates and showed that the interaction is preferably done at the hydrophobic regions of the fibrils. Also, the researchers performed "in vitro" assays to experimentally validate the candidates. They found that the four tripeptides had significant depolymerizing activity and their DC50 values were in the micromolar range, confirming the results obtained in the "in silico" analysis. This method describes a set of tripeptides with high binding affinity to amyloid beta fibrils and the mechanisms of these interactions that lead to amyloid beta depolymerization and that could be a potential therapeutic approach for Alzheimer's disease that can be further tested in future studies.
In silico and in vitro study of binding affinity of tripeptides to amyloid β fibrils: implications for Alzheimer’s disease
Mai Suan Li(1), Zuzana Gazova(2)
Added on: 08-15-2021
[1] https://pubs.acs.org/doi/10.1021/acs.jpcb.5b00006[2] https://data.jrc.ec.europa.eu/dataset/a8fd26ef-b113-47ab-92ba-fd2be449c7eb
