title: Protection against Abeta-induced memory loss by tripeptide D-Arg-L-Glu-L-Arg.
abstract: The molecular and cellular mechanisms underlying the memory deficits in Alzheimer's disease are increasingly thought to be associated with faulty processing of amyloid precursor protein. Following our earlier findings that it is possible to use the tripeptide RER (NH2-D-Arg-L-Glu-L-Arg-COOH, derived from the external domain of amyloid precursor protein) to rescue memory in animal models, we report here that the diasteromeric (D/L) form of the acetylated tripeptide RER protects against Abeta-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 before training. The tripeptide readily crosses the blood-brain barrier, binds to membrane receptor sites in the brain and is without adverse effects on general behaviour. We discuss this finding in the context of other studies of the importance of peptides containing D-amino acids, and conclude that these RER-related peptides may form the basis for a potential therapeutic agent in the early stages of Alzheimer's disease.
authors.affiliation: Department of Biological Sciences, the Open University, Milton Keynes, UK. r.mileusnic@open.ac.uk
authors.forename: Radmila
authors.initials: R
authors.lastname: Mileusnic
authors.forename: Christine
authors.initials: C
authors.lastname: Lancashire
authors.forename: Jonathan
authors.initials: J
authors.lastname: Clark
authors.forename: Steven P R
authors.initials: SP
authors.lastname: Rose
mesh_terms: D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism; D002645:Chickens; D003216:Conditioning, Operant / Q000187:drug effects; D007267:Injections; D007536:Isomerism; D008569:Memory Disorders / Q000139:chemically induced* / Q000517:prevention & control*; D018696:Neuroprotective Agents; D009842:Oligopeptides / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D013237:Stereoisomerism; D014018:Tissue Distribution
chemical_list: D016229:Amyloid beta-Peptides; D018696:Neuroprotective Agents; D009842:Oligopeptides; C521328:arginyl-glutamyl-arginine