Journal
NEUROBIOLOGY OF DISEASE
Volume 18, Issue 3, Pages 499-508Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nbd.2004.12.008
Keywords
Alzheimer's disease; beta-amyloid 1-42; neuroprotective pentapeptides; electrophysiology; microiontophoresis; single-unit activity; hippocampus; transmission etectron microscopy; EPSP; primary motor cortex
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Short fragments and fragment analogues of beta-amyloid 1-42 peptide (A beta 1-42) display a protective effect against A beta-mediated neurotoxicity. After consideration of our earlier results with in vitro bioassay of synthetic A beta-recognition peptides and toxic fibrillar amyloids, five pentapeptides were selected as putative neuroprotective agents: Phe-Arg-His-Asp-Ser amide (A beta 4-8) and Gly-Arg-His-Asp-Ser amide (an analogue of A beta 4-8), Leu-Pro-Tyr-Phe-Asp amide (an analogue of A beta 17-21), Arg-Ile-Ile-Gly-Leu amide (an analogue of A beta 30-34), and Arg-Val-Val-Ile-Ala amide (an analogue of A beta 38-42). In vitro electrophysiological experiments on rat brain slices demonstrated that four of these peptides counteracted with the field excitatory postsynaptic potential-attenuating effect of A beta 1-42; only Arg-Val-Val-Ile-Ala amide proved inactive. In in vivo experiments using extracellular single-unit recordings combined with iontophoresis, all these pentapeptides except Arg-Val-Val-Ile-Ala amide protected neurons from the NMDA response-enhancing effect of A beta 1-42 in the hippocampal CA1 region. These results suggest that A beta recognition sequences may serve as leads for the design of novel neuroprotective compounds. (c) 2005 Elsevier Inc. All rights reserved.
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