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.TwopeptidesnamedNL1L4 and L1L4 demonstrated goodNGFagonist activity at a concentration as low as 3M. 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.

A New Nerve Growth Factor-Mimetic Peptide Active on Neuropathic Pain in Rats / Colangelo, A. M.; Bianco, M. R.; Vitagliano, L.; Cavaliere, C.; Cirillo, G.; De Gioia, L.; Diana, D.; Colombo, D.; Redaelli, C.; Zaccaro, L.; Morelli, Giancarlo; Papa, M.; Sarmientos, P.; Alberghina, L.; Martegani, E.. - In: THE JOURNAL OF NEUROSCIENCE. - ISSN 0270-6474. - STAMPA. - 28:(2008), pp. 2698-2709.

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

D. Diana;MORELLI, GIANCARLO;
2008

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.TwopeptidesnamedNL1L4 and L1L4 demonstrated goodNGFagonist activity at a concentration as low as 3M. 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.
2008
A New Nerve Growth Factor-Mimetic Peptide Active on Neuropathic Pain in Rats / Colangelo, A. M.; Bianco, M. R.; Vitagliano, L.; Cavaliere, C.; Cirillo, G.; De Gioia, L.; Diana, D.; Colombo, D.; Redaelli, C.; Zaccaro, L.; Morelli, Giancarlo; Papa, M.; Sarmientos, P.; Alberghina, L.; Martegani, E.. - In: THE JOURNAL OF NEUROSCIENCE. - ISSN 0270-6474. - STAMPA. - 28:(2008), pp. 2698-2709.
File in questo prodotto:
File Dimensione Formato  
J.Neurosci.2008.pdf

non disponibili

Tipologia: Documento in Post-print
Licenza: Accesso privato/ristretto
Dimensione 736.69 kB
Formato Adobe PDF
736.69 kB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/316714
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 112
  • ???jsp.display-item.citation.isi??? 101
social impact