Mileusnic Radmila, Lancashire Christine, Clark Jonathan, Rose Steven P R
Department of Biological Sciences, the Open University, Milton Keynes, UK.
Behav Pharmacol. 2007 May;18(3):231-8. doi: 10.1097/FBP.0b013e32814fcde9.
The molecular and cellular mechanisms underlying the memory deficits in Alzheimer's disease are increasingly thought to be associated with faulty processing of amyloid precursor protein. Following our earlier findings that it is possible to use the tripeptide RER (NH2-D-Arg-L-Glu-L-Arg-COOH, derived from the external domain of amyloid precursor protein) to rescue memory in animal models, we report here that the diasteromeric (D/L) form of the acetylated tripeptide RER protects against Abeta-induced memory loss for a passive avoidance task in young chicks and enhances retention for a weak version of the task when injected peripherally up to 12 h before training. The tripeptide readily crosses the blood-brain barrier, binds to membrane receptor sites in the brain and is without adverse effects on general behaviour. We discuss this finding in the context of other studies of the importance of peptides containing D-amino acids, and conclude that these RER-related peptides may form the basis for a potential therapeutic agent in the early stages of Alzheimer's disease.
越来越多的研究认为，阿尔茨海默病记忆缺陷背后的分子和细胞机制与淀粉样前体蛋白的错误加工有关。基于我们之前的发现，即可以使用三肽RER（NH2-D-Arg-L-Glu-L-Arg-COOH，源自淀粉样前体蛋白的外部结构域）来挽救动物模型中的记忆，我们在此报告，乙酰化三肽RER的非对映体（D/L）形式可保护幼雏在被动回避任务中免受β-淀粉样蛋白诱导的记忆丧失，并且在训练前长达12小时外周注射时，可增强对较弱版本任务的记忆保持。该三肽能够轻易穿过血脑屏障，与大脑中的膜受体位点结合，并且对一般行为没有不良影响。我们结合其他关于含D-氨基酸肽重要性的研究来讨论这一发现，并得出结论，这些与RER相关的肽可能构成阿尔茨海默病早期潜在治疗药物的基础。
