Pentapeptides derived from A beta 1-42 protect modulatory effect of A beta fibrils - an in vivo electrophysiological study

Szegedi, Viktor and Fülöp, Lívia and Farkas, Tamás and Rózsa, E. and Robotka, H. and Kis, Zsolt and Penke, Z. and Horváth, Szatmár and Molnár, Z. and Datki, Zsolt and Soós, Katalin and Toldi, József and Budai, D. and Zarándi, Márta and Penke, Botond (2005) Pentapeptides derived from A beta 1-42 protect modulatory effect of A beta fibrils - an in vivo electrophysiological study. Neurobiology of Disease, 18 (3). pp. 499-508. ISSN 0969-9961

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Abstract

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.

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