Effect Of Functioncalized Gold Nanoparticles And Cu²⁺-mediated Amyloid Seeds On The Inhibition Of Amyloid Aggregation

The accumulation of aggregated amyloid-β（Aβ）protein is considered to be one of the most important factors that could affect Alzheimer’s disease（AD）.Therefore,the inhibition of Aβaggregation has been an important strategy for the prevention and treatment of AD.Researches have showed that the formation of a nucleus,in Aβaggregation progress,firstly requires a series of monomeric Aβassociation steps.Once the critical concentration of nucleus is reached,the nucleus acts as a catalyst and extends to form larger formers.With increased concentration of monomeric Aβ,the Aβstructures are referred to as protofibrils,which interweave to form fibrils and further polymerize as aggregation deposit.This progress is also called the secondary nucleation model of the Aβaggregation.It is very important to understand inhibitors or metal irons how to influence the Aβaggregation progress,which contributes to knowing the pathogenesis of AD better and designing more effective amyloid inhibitors.On the basis of previous study,we chose the most effective peptide VCD10 to explore the effects of different concentrations of VCD10 on kinetics of Aβfibrillation and seeded Aβfibrillation.Furthermore,we studied the characteristics of VCD10@AuNP on the inhibitory effects of Aβaggregation.What’s more,we have investigated the different Aβseeds mediated at different concentrations of Cu²⁺and their effects on Aβfibrillation.The results showed that both VCD10 and VCD10@AuNP could inhibit Aβaggregation,prolong the lag phage of Aβ40aggregation,and inhibit the secondary nucleation of Aβ40 fibrillation with dose-dependent inhibition ability.In addition,with increasing Cu²⁺concentrations,these findings suggested that morphology of the seeds shifted from fibrillar to spherical aggregates,and the metal:peptide stoichiometry in the seeds increased as well.However,although mediated by different Cu²⁺concentrations,the seeds could promoted the nucleation of Aβfibrillation.From the above research results,the characteristics of VCD10 and VCD10@AuNP on Aβaggregation and of metal irons on Aβfibrillation were further clarified,thus laying theoretical and experimental foundations for further understanding the mechanism of Aβaggregation and developing Aβaggregation inhibitors.