Pentapeptides derived from Aβ1-42 protect neurons from the modulatory effect of Aβ fibrils-an in vitro and in vivo electrophysiological study

V. Szegedi, L. Fülöp, T. Farkas, E. Rózsa, H. Robotka, Z. Kis, Z. Penke, S. Horváth, Z. Molnár, Z. Datki, K. Soós, J. Toldi, D. Budai, M. Zarándi, B. Penke

Research output: Article

21 Citations (Scopus)

Abstract

Short fragments and fragment analogues of beta-amyloid 1-42 peptide (Aβ1-42) display a protective effect against Aβ-mediated neurotoxicity. After consideration of our earlier results with in vitro bioassay of synthetic Aβ-recognition peptides and toxic fibrillar amyloids, five pentapeptides were selected as putative neuroprotective agents: Phe-Arg-His-Asp-Ser amide (Aβ4-8) and Gly-Arg-His-Asp-Ser amide (an analogue of Aβ4-8), Leu-Pro-Tyr-Phe-Asp amide (an analogue of Aβ17-21), Arg-Ile-Ile-Gly-Leu amide (an analogue of Aβ30-34), and Arg-Val-Val-Ile-Ala amide (an analogue of Aβ38-42). In vitro electrophysiological experiments on rat brain slices demonstrated that four of these peptides counteracted with the field excitatory postsynaptic potential-attenuating effect of Aβ1-42; 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 Aβ1-42 in the hippocampal CA1 region. These results suggest that Aβ recognition sequences may serve as leads for the design of novel neuroprotective compounds.

Original languageEnglish
Pages (from-to)499-508
Number of pages10
JournalNeurobiology of Disease
Volume18
Issue number3
DOIs
Publication statusPublished - ápr. 2005

    Fingerprint

ASJC Scopus subject areas

  • Neurology

Cite this