LPYFDa neutralizes amyloid-β-induced memory impairment and toxicity

Ivica Granic, Marcelo F. Masman, Cornelis Mulder, Ingrid M. Nijholt, Pieter J.W. Naude, Ammerins De Haan, Emöke Borbély, Botond Penke, Paul G.M. Luiten, Ulrich L.M. Eisel

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Misfolding, oligomerization, and aggregation of the amyloid-β (Aβ) peptide is widely recognized as a central event in the pathogenesis of Alzheimer's disease (AD). Recent studies have identified soluble Aβ oligomers as the main pathogenic agents and provided evidence that such oligomeric Aβ aggregates are neurotoxic, disrupt synaptic plasticity, and inhibit long-term potentiation. A promising therapeutic strategy in the battle against AD is the application of short synthetic peptides which are designed to bind to specific Aβ-regions thereby neutralizing or interfering with the devastating properties of oligomeric Aβ species. In the present study, we investigated the neuroprotective properties of the amyloid sequence derived pentapeptide LPYFDa in vitro as well as its memory preserving capacity against Aβ42;-induced learning deficits in vivo. In vitro we showed that neurons in culture treated with LPYFDa are protected against Aβ42-induced cell death. Moreover, in vivo LPYFDa prevented memory impairment tested in a contextual fear conditioning paradigm in mice after bilateral intrahippocampal Aβ42 injections. We thus showed for the first time that an anti-amyloid peptide like LPYFDa can preserve memory by reverting Aβ42 oligomer-induced learning deficits.

Original languageEnglish
Pages (from-to)991-1005
Number of pages15
JournalJournal of Alzheimer's Disease
Volume19
Issue number3
DOIs
Publication statusPublished - 2010

Keywords

  • Alzheimer's disease
  • Amyloid-β oligomers
  • Behavioral tests
  • Circular dichroism spectrometry
  • Fear conditioning
  • Hippocampus
  • Molecular modeling
  • Neuroprotection
  • Primary cortical neurons
  • β-sheet breaker peptides

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health

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  • Cite this

    Granic, I., Masman, M. F., Mulder, C., Nijholt, I. M., Naude, P. J. W., De Haan, A., Borbély, E., Penke, B., Luiten, P. G. M., & Eisel, U. L. M. (2010). LPYFDa neutralizes amyloid-β-induced memory impairment and toxicity. Journal of Alzheimer's Disease, 19(3), 991-1005. https://doi.org/10.3233/JAD-2010-1297