Beta-sheet breaker peptide prevents Abeta-induced spatial memory impairments with partial reduction of amyloid deposits.
Current evidence supports the notion that beta-amyloid deposits or Abeta intermediates may be responsible for the pathogenesis in Alzheimer's disease (AD) patients. In the present work, we have assessed the neuroprotective effect of the chronic intraperitoneal administration of a five-amino-acid beta-sheet breaker peptide (iAbeta5p) on the rat behavioral deficit induced by the intrahippocampal Abeta-fibrils injection. At 1 month after the injection, animals showed a partial reduction of the amyloid deposits formed and a decreased astrocytic response around the injection site. More importantly, we report that following the iAbeta5p treatment, hippocampal-dependent spatial learning paradigms, including the standard Morris water maze and a working memory analysis, showed a significant prevention from impairments induced by Abeta deposits in the dorsal hippocampus. Thus, it is possible that a noninvasive treatment such as the one presented here with beta-sheet breaker peptides may be used as a potential therapy for AD patients.
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Centro FONDAP de Regulación Celular y Patología Joaquín V Luco, MIFAB, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile.
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D000544:Alzheimer Disease; D000682:Amyloid / Q000032:analysis; D016229:Amyloid beta-Peptides / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity*; D000686:Amyloidosis / Q000473:pathology* / Q000523:psychology; D000818:Animals; D001253:Astrocytes / Q000473:pathology; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D007267:Injections; D007274:Injections, Intraperitoneal; D008297:Male; D018782:Maze Learning / Q000187:drug effects* / Q000502:physiology; D008569:Memory Disorders / Q000139:chemically induced / Q000517:prevention & control*; D018697:Nootropic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D010446:Peptide Fragments / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity*; D017433:Protein Structure, Secondary / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time; D013037:Spatial Behavior / Q000187:drug effects* / Q000502:physiology; D013238:Stereotaxic Techniques
D000682:Amyloid; D016229:Amyloid beta-Peptides; D018697:Nootropic Agents; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); C474023:iAbeta5 peptide