期刊
JOURNAL OF NEUROCHEMISTRY
卷 118, 期 4, 页码 616-625出版社
WILEY
DOI: 10.1111/j.1471-4159.2011.07193.x
关键词
CRMP2; memory; peptides; RER binding partners; sAPP
资金
- EUSAPharma
The diasteromeric (D/L) form of the acetylated tripeptide rER (NH2-D-arg-L-glu-D-arg-COOH), derived from the external domain of amyloid precursor protein, protects against amyloid-beta 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 prior to training. The tripeptide readily crosses the blood-brain barrier, binds to receptor sites in the brain and is without adverse effects on general behaviour. The mechanisms of its action are unknown, as are its target molecules/pathways. Here, we report the binding partners for Ac-rER are collapsin response mediator protein 2 (CRMP2), syntaxin binding protein 1 and heat shock protein 70. Behavioural studies of the effects of Ac-rER on memory retention confirmed that the effect of Ac-rER is mediated via CRMP2, as anti-CRMP2 antibodies if injected intracranially 30 min pre-training, induced amnesia for the passive avoidance task. However, Ac-rER, if injected prior to the anti-CRMP2, rescues the memory deficits induced by anti-CRMP2 antibodies. As CRMP2 is placed at the junction of many different cellular processes during brain development and in adult neuronal plasticity as well as being implicated in Alzheimer's disease, this strengthens the claim that Ac-rER may be a potential therapeutic agent in Alzheimer's disease, although its precise mode of action remains to be elucidated.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据