Sun Xicui, Duan Songwei, Cao Anna, Villagomez Bryan, Lin Runxuan, Chen Hongxia, Pi Liya, Ren Bin, Chen Rong, Chen Minjie, Ying Zhekang, Fang Shenyun, Cao Qi
Department of Neurology, Sun Yat-sen University, Guangzhou, Guangdong, China.
Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.
J Alzheimers Dis Rep. 2021 Jun 8;5(1):479-495. doi: 10.3233/ADR-210012. eCollection 2021.
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 aggregating inhibition and Aβ clearance.
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.
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.
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.
目前对淀粉样β蛋白（Aβ）聚集和毒性的理解为治疗阿尔茨海默病（AD）提供了大量药物；然而，最有前景的治疗策略之一是三肽。
本研究旨在研究那些具有抑制Aβ聚集和清除Aβ潜力的三肽，如精氨酸-精氨酸-色氨酸（RRY）。
在本研究中，整合了[此处原文缺失相关内容]、[此处原文缺失相关内容]和[此处原文缺失相关内容]研究，用于筛选与Aβ结合的三肽，然后评估其对Aβ聚集的抑制作用，最后评估其对认知缺陷的挽救作用。
在[此处原文缺失相关内容]模拟中，分子对接和分子动力学确定了七种排名靠前的三肽可与Aβ结合并形成稳定复合物。圆二色性、硫代黄素T检测和透射电子显微镜表明这七种三肽可能抑制Aβ聚集。在[此处原文缺失相关内容]研究中，使用了莫里斯水迷宫、酶联免疫吸附测定和荧光素酶染色，数据表明RRY能够挽救转基因小鼠模型中Aβ诱导的认知缺陷，降低Aβ负荷并增加树突棘。
三项连续研究的这些趋同结果使我们得出结论，RRY是Aβ聚集的首选抑制剂，也是治疗Aβ诱导的认知缺陷的药物。
