Mileusnic Radmila, Rose Steven
Department of Life Sciences, Faculty of Sciences, The Open University, Milton Keynes, MK7 6AA, UK.
Int J Alzheimers Dis. 2010 Jul 18;2010:180734. doi: 10.4061/2010/180734.
While animal experiments have contributed much to our understanding of the mechanisms of Alzheimer's disease (AD), their value in predicting the effectiveness of treatment strategies in clinical trials has remained controversial. The disparity between the results obtained in animal models and clinical trials may in part be explained by limitations of the models and species-specific differences. We propose that one trial passive avoidance in the day-old chick is a useful system to study AD because of the close sequence homologies of chick and human amyloid precursor protein (APP). In the chick, APP is essential for memory consolidation, and disrupting its synthesis or structure results in amnesia. RER, a tripeptide sequence corresponding to part of the growth domain of APP, can restore memory loss and act as a cognitive enhancer. We suggest that RER and its homologues may form the basis for potential pharmacological protection against memory loss in AD.
虽然动物实验对我们理解阿尔茨海默病（AD）的发病机制有很大帮助，但其在预测临床试验中治疗策略有效性方面的价值一直存在争议。动物模型和临床试验结果之间的差异部分可能是由于模型的局限性和物种特异性差异造成的。我们提出，由于雏鸡和人类淀粉样前体蛋白（APP）的序列同源性很高，雏鸡一日龄时的单次被动回避试验是研究AD的一个有用系统。在雏鸡中，APP对记忆巩固至关重要，破坏其合成或结构会导致失忆。RER是一种与APP生长结构域部分相对应的三肽序列，它可以恢复记忆丧失并作为一种认知增强剂。我们认为，RER及其同源物可能构成针对AD记忆丧失的潜在药物保护的基础。
