RRY Inhibits Amyloid-β Peptide Aggregation and Neurotoxicity.

Background: 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.

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

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

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

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