Affiliations: [a] Department of Medical Chemistry, JGYTFK, University of Szeged, Szeged, Hungary | [b] Department of Pharmacodynamics and Biopharmacy, JGYTFK, University of Szeged, Szeged, Hungary | [c] Department of Biology, JGYTFK, University of Szeged, Szeged, Hungary | [d] Supramolecular and Nanostructural Research Group, Hungarian Academy of Sciences, Szeged, Hungary | [e] Bay Zoltán Foundation for Applied Research – BAYGEN, Szeged, Hungary
Correspondence:
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Corresponding author: Viktor Szegedi PhD., Bay Zoltán Foundation for Applied Research – BAYGEN, Közép fasor 47, Szeged H-6726, Hungary. Tel.: +36 62 545135; Fax: +36 62 545971; E-mail: szegediv@baygen.hu.
Note: [] Communicated by Ved Chauhan
Abstract: 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 Aβ1–42 and protects neurons against the toxic effects of aggregated Aβ1–42 both in vitro and in vivo. Our previous work indicated that the in vivo ejection of fibrillar Aβ1–42 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 Aβ1–42 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 Aβ1–42 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.
