An Intraperitoneally Administered Pentapeptide Protects Against A beta(1-42) Induced Neuronal Excitation In Vivo

作者：Juhasz Gabor; Marki Arpad; Vass Gabriella; Fulop Livia; Budai Denes; Penke Botond; Falkay Gyoergy; Szegedi Viktor^*

来源：Journal of Alzheimer's Disease, 2009, 16(1): 189-196.

DOI：10.3233/JAD-2009-0947

• Alzheimer's disease
• hippocampus
• neuroprotection
• NMDA
• protective pentapeptide
• single-unit

The underlying cause of Alzheimer's disease (AD) is thought to be the accumulation and aggregation of a misfolded protein, amyloid-beta (A beta). A promising strategy against AD is the application of protective, peptide-based neuroprotective agents that selectively bind to A beta. We recently described a pentapeptide, LPYFDa, which recognizes A beta(1-42) and protects neurons against the toxic effects of aggregated A beta(1-42) both in vitro and in vivo. Our previous work indicated that the in vivo ejection of fibrillar A beta(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 A beta(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 A beta(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.

• 出版日期2009