A new nerve growth factor-mimetic peptide active on neuropathic pain in rats

Anna Maria Colangelo, Maria Rosaria Bianco, Luigi Vitagliano, Carlo Cavaliere, Giovanni Cirillo, Luca De Gioia, Donatella Diana, Daniele Colombo, Cristina Redaelli, Laura Zaccaro, Giancarlo Morelli, Michele Papa, Paolo Sarmientos, Lilia Alberghina, Enzo Martegani

Research output: Contribution to journalArticlepeer-review

Abstract

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 μM. 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.

Original languageEnglish
Pages (from-to)2698-2709
Number of pages12
JournalJournal of Neuroscience
Volume28
Issue number11
DOIs
Publication statusPublished - Mar 12 2008

Keywords

  • Bioactive peptides
  • Gliosis
  • Neuropathic pain
  • NGF
  • NMR structure
  • TrkA

ASJC Scopus subject areas

  • Neuroscience(all)

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