A New Nerve Growth Factor-Mimetic Peptide Active on Neuropathic Pain in Rats

Analysis of the structure of nerve growth factor (NGF)-tyrosine kinase receptor A (TrkA) complex, site-directed mutagenesis studies and results from chemical modification of amino acid residues have identified loop 1, loop 4, and the N-terminal region of the NGF molecule as the most relevant for its...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:The Journal of neuroscience 2008-03, Vol.28 (11), p.2698-2709
Hauptverfasser: Colangelo, Anna Maria, Bianco, Maria Rosaria, Vitagliano, Luigi, Cavaliere, Carlo, Cirillo, Giovanni, De Gioia, Luca, Diana, Donatella, Colombo, Daniele, Redaelli, Cristina, Zaccaro, Laura, Morelli, Giancarlo, Papa, Michele, Sarmientos, Paolo, Alberghina, Lilia, Martegani, Enzo
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung:Analysis of the structure of nerve growth factor (NGF)-tyrosine kinase receptor A (TrkA) complex, site-directed mutagenesis studies and results from chemical modification of amino acid residues have identified loop 1, loop 4, and the N-terminal region of the NGF molecule as the most relevant for its biological activity. We synthesized several peptides mimicking the two loops (1 and 4) linked together with an appropriate spacer, with or without the N-terminal region. Two peptides named NL1L4 and L1L4 demonstrated good NGF agonist activity at a concentration as low as 3 mum. They induced differentiation of chick dorsal root ganglia and stimulated tyrosine phosphorylation of TrkA, but not TrkB, receptor. In addition L1L4 was able to induce differentiation of PC12 cells. More interestingly, the peptide with the highest "in vitro" activity (L1L4) was shown to reduce neuropathic behavior and restore neuronal function in a rat model of peripheral neuropathic pain, thereby suggesting a potential therapeutic role for this NGF-mimetic peptide.
ISSN:0270-6474
1529-2401
DOI:10.1523/JNEUROSCI.5201-07.2008