RRY Inhibits Amyloid-β_1-42 Peptide Aggregation and Neurotoxicity

Current understanding of amyloid-β protein (Aβ) aggregation and toxicity provides an extensive list of drugs for treating Alzheimer's disease (AD); however, one of the most promising strategies for its treatment has been tri-peptides.

The aim of this study is to examine those tri-peptides, such as Arg-Arg-Try (RRY), which have the potential of Aβ_1-42 aggregating inhibition and Aβ clearance.

In the present study, in silico, in vitro, and in vivo studies were integrated for screening tri-peptides binding to Aβ, then evaluating its inhibition of aggregation of Aβ, and finally its rescuing cognitive deficit.

In the in silico simulations, molecular docking and molecular dynamics determined that seven top-ranking tri-peptides could bind to Aβ_1-42 and form stable complexes. Circular dichroism, ThT assay, and transmission electron microscope indicated the seven tri-peptides might inhibit the aggregation of Aβ_1-42 in vitro. In the in vivo studies, Morris water maze, ELISA, and Diolistic staining were used, and data showed that RRY was capable of rescuing the Aβ_1-42-induced cognitive deficit, reducing the Aβ_1-42 load and increasing the dendritic spines in the transgenic mouse model.

Such converging outcomes from three consecutive studies lead us to conclude that RRY is a preferred inhibitor of Aβ_1-42 aggregation and treatment for Aβ-induced cognitive deficit.