An intraperitoneally administered pentapeptide protects against Aβ1-42 induced neuronal excitation in vivo

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The underlying cause of Alzheimer's disease (AD) is thought to be the accumulation and aggregation of a misfolded protein, amyloid-β (Aβ). A promising strategy against AD is the application of protective, peptide-based neuroprotective agents that selectively bind to Aβ. We recently described a pentapeptide, LPYFDa, which recognizes Aβ-{1-42} and protects neurons against the toxic effects of aggregated Aβ-{1-42} both in vitro and in vivo. Our previous work indicated that the in vivo ejection of fibrillar Aβ-{1-42} into the hippocampal CA1 region resulted in a massive increase in the NMDA-evoked neuronal firing rate. Our current aim was to study whether intraperitoneally administered LPYFDa is capable of protecting against the synaptotoxic action of fibrillar Aβ-{1-42} administered by iontophoresis. Our investigations of the in vivo biodistribution of tritium-labelled LPYFDa and single-unit electrophysiology revealed that LPYFDa readily crosses the blood-brain barrier, and protects the synapses against the excitatory action of fibrillar Aβ-{1-42} in a relatively wide temporal window in rat. This pentapeptide may serve as a lead compound for the design of novel drug candidates for the prevention of AD.

Original languageEnglish
Pages (from-to)189-196
Number of pages8
JournalJournal of Alzheimer's Disease
Issue number1
Publication statusPublished - 2009


ASJC Scopus subject areas

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

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