Author
Sun, XicuiDuan, Songwei
Cao, Anna
Villagomez, Bryan
Lin, Runxuan
Chen, Hongxia
Pi, Liya
Ren, Bin
Chen, Rong
Chen, Minjie
Ying, Zhekang
Fang, Shenyun
Cao, Qi
Date
2021-06-08Journal
Journal of Alzheimer's Disease ReportsPublisher
IOS PressType
Article
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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 Aβ1-42 aggregating inhibition and Aβ clearance. Methods: 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. Results: In the in silico simulations, molecular docking and molecular dynamics determined that seven top-ranking tri-peptides could bind to Aβ1-42 and form stable complexes. Circular dichroism, ThT assay, and transmission electron microscope indicated the seven tri-peptides might inhibit the aggregation of Aβ1-42 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 Aβ1-42-induced cognitive deficit, reducing the Aβ1-42 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 Aβ1-42 aggregation and treatment for Aβ-induced cognitive deficit.Rights/Terms
© 2021 – The authors. Published by IOS Press.Identifier to cite or link to this item
http://hdl.handle.net/10713/16365ae974a485f413a2113503eed53cd6c53
10.3233/ADR-210012
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