TY - JOUR
T1 - A new nerve growth factor-mimetic peptide active on neuropathic pain in rats
AU - Colangelo, Anna Maria
AU - Bianco, Maria Rosaria
AU - Vitagliano, Luigi
AU - Cavaliere, Carlo
AU - Cirillo, Giovanni
AU - De Gioia, Luca
AU - Diana, Donatella
AU - Colombo, Daniele
AU - Redaelli, Cristina
AU - Zaccaro, Laura
AU - Morelli, Giancarlo
AU - Papa, Michele
AU - Sarmientos, Paolo
AU - Alberghina, Lilia
AU - Martegani, Enzo
PY - 2008/3/12
Y1 - 2008/3/12
N2 - 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.
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.
KW - Bioactive peptides
KW - Gliosis
KW - Neuropathic pain
KW - NGF
KW - NMR structure
KW - TrkA
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UR - http://www.scopus.com/inward/citedby.url?scp=40849083920&partnerID=8YFLogxK
U2 - 10.1523/JNEUROSCI.5201-07.2008
DO - 10.1523/JNEUROSCI.5201-07.2008
M3 - Article
C2 - 18337399
AN - SCOPUS:40849083920
VL - 28
SP - 2698
EP - 2709
JO - Journal of Neuroscience
JF - Journal of Neuroscience
SN - 0270-6474
IS - 11
ER -