The memory enhancing effect of the APP-derived tripeptide Ac-rER is mediated through CRMP2

Mileusnic, Radmila and Rose, Steven P. R. (2011). The memory enhancing effect of the APP-derived tripeptide Ac-rER is mediated through CRMP2. Journal of Neurochemistry, 118(4) pp. 616–625.

DOI: https://doi.org/10.1111/j.1471-4159.2011.07193.x

Abstract

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-b induced memory loss for a passive avoidance task inyoung chicks and enhances retention for a weak version of thetask 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 AcrER 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.

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