RT Journal Article
SR Electronic
T1 A New Nerve Growth Factor-Mimetic Peptide Active on Neuropathic Pain in Rats
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 2698
OP 2709
DO 10.1523/JNEUROSCI.5201-07.2008
VO 28
IS 11
A1 Anna Maria Colangelo
A1 Maria Rosaria Bianco
A1 Luigi Vitagliano
A1 Carlo Cavaliere
A1 Giovanni Cirillo
A1 Luca De Gioia
A1 Donatella Diana
A1 Daniele Colombo
A1 Cristina Redaelli
A1 Laura Zaccaro
A1 Giancarlo Morelli
A1 Michele Papa
A1 Paolo Sarmientos
A1 Lilia Alberghina
A1 Enzo Martegani
YR 2008
UL http://www.jneurosci.org/content/28/11/2698.abstract
AB 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.