The peptide sequence Arg-Glu-Arg, present in the amyloid precursor protein, protects against memory loss caused by A beta and acts as a cognitive enhancer.
Amino acid sequences containing the palindromic tripeptide RER, matching amino acids 328-330 of the amyloid precursor protein APP, when injected intracerebrally prior to or just after training, protect against memory loss induced by amyloid-beta (A beta) in a one-trial passive avoidance task in the young chick. RER also acts as a cognitive enhancer, strengthening memory for a weak version of the task. N-terminal acylation of RER protects it against rapid degradation, and AcRER is effective in restoring memory if administered peripherally. Biotinylated RER binds to chick neuronal perikarya in an APP-displaceable manner via 66 and approximately 110 kDa neuronal cell membrane proteins. We suggest that RER binding is likely to exert effects on memory retention via receptor-mediated events that include activation of second messenger pathways. These findings suggest that RER and its derivatives may offer a novel approach to enhancing the neuroprotective effects of APP and alleviating the effects of memory loss in the early stages of Alzheimer's disease.
Mileusnic
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R
Brain and Behaviour Research Group, The Open University, Milton Keynes, MK7 6AA, UK. r.mileusnic@open.ac.uk
Lancashire
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CL
Rose
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SP
D000647:Amnesia / Q000139:chemically induced / Q000188:drug therapy*; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001362:Avoidance Learning / Q000187:drug effects; D001665:Binding Sites; D001667:Binding, Competitive; D019921:Biotinylation / Q000379:methods; D015153:Blotting, Western / Q000379:methods; D002452:Cell Count / Q000379:methods; D002462:Cell Membrane / Q000187:drug effects; D002645:Chickens; D004305:Dose-Response Relationship, Drug; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D018698:Glutamic Acid / Q000494:pharmacology; D007150:Immunohistochemistry / Q000379:methods; D007276:Injections, Intraventricular / Q000379:methods; D008569:Memory Disorders / Q000517:prevention & control*; D018697:Nootropic Agents / Q000627:therapeutic use*; D009842:Oligopeptides / Q000627:therapeutic use*; D010446:Peptide Fragments / Q000494:pharmacology; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D016548:Prosencephalon / Q000166:cytology / Q000187:drug effects
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D005904:Glial Fibrillary Acidic Protein; D018697:Nootropic Agents; D009842:Oligopeptides; D010446:Peptide Fragments; C092395:amyloid beta-protein (12-28); D018698:Glutamic Acid; D010751:Phosphopyruvate Hydratase