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.

Abstract

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.

• Authors: R Mileusnic, C L Lancashire, S P R Rose
• Journal: The European journal of neuroscience (Eur J Neurosci) Vol. 19 Issue 7 Pg. 1933-8 (Apr 2004) ISSN: 0953-816X [Print] France
• PMID: 15078567 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Amyloid beta-Peptides
• Amyloid beta-Protein Precursor
• Glial Fibrillary Acidic Protein
• Nootropic Agents
• Oligopeptides
• Peptide Fragments
• amyloid beta-protein (12-28)
• Glutamic Acid
• Phosphopyruvate Hydratase

Topics

• Amnesia (chemically induced, drug therapy)
• Amyloid beta-Peptides
• Amyloid beta-Protein Precursor (chemistry, metabolism)
• Animals
• Animals, Newborn
• Avoidance Learning (drug effects)
• Binding Sites
• Binding, Competitive
• Biotinylation (methods)
• Blotting, Western (methods)
• Cell Count (methods)
• Cell Membrane (drug effects)
• Chickens
• Dose-Response Relationship, Drug
• Glial Fibrillary Acidic Protein (metabolism)
• Glutamic Acid (pharmacology)
• Immunohistochemistry (methods)
• Injections, Intraventricular (methods)
• Memory Disorders (prevention & control)
• Nootropic Agents (therapeutic use)
• Oligopeptides (therapeutic use)
• Peptide Fragments (pharmacology)
• Phosphopyruvate Hydratase (metabolism)
• Prosencephalon (cytology, drug effects)