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

J. Neurochem. (2011) 118, 616–625. 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‐β induced memory loss for a passive avoidance task in young chicks and enhances reten...

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Published in:	Journal of neurochemistry 2011-08, Vol.118 (4), p.616-625
Main Authors:	Mileusnic, Radmila, Rose, Steven P. R.
Format:	Article
Language:	eng
Subjects:	Alzheimer's disease Amnesia Amnesia - chemically induced Amnesia - prevention & control Amyloid beta-Protein Precursor - chemistry Amyloid beta-Protein Precursor - pharmacology Amyloid precursor protein Animals Antibodies Avoidance Learning - drug effects beta -Amyloid Biological and medical sciences Biotinylation Blood-brain barrier Blotting, Western Brain Brain Chemistry Chickens Collapsin response mediator protein 2 Conditioning, Operant - drug effects Contrast Media CRMP2 Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases Disorders of higher nervous function. Focal brain diseases. Central vestibular syndrome and deafness. Brain stem syndromes double prime L form Electrophoresis, Polyacrylamide Gel Fluorescein HSC70 Heat-Shock Proteins - metabolism Hsp70 protein Humans Immunoelectrophoresis, Two-Dimensional Immunohistochemistry Injections, Intraventricular Intercellular Signaling Peptides and Proteins - physiology Medical sciences Memory Memory - drug effects Munc18 Proteins - metabolism Nerve Tissue Proteins - antagonists & inhibitors Nerve Tissue Proteins - physiology Nervous system (semeiology, syndromes) Neurochemistry Neurodegenerative diseases Neurology Oligopeptides - pharmacology Peptides Plasticity (neural) Protein Binding Proteomics RER binding partners sAPP Side effects Syntaxin
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Summary:	J. Neurochem. (2011) 118, 616–625. 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‐β 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.
ISSN:	0022-3042 1471-4159