Journal
JOURNAL OF NEUROSCIENCE
Volume 28, Issue 11, Pages 2698-2709Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.5201-07.2008
Keywords
NGF; bioactive peptides; NMR structure; neuropathic pain; gliosis; TrkA
Categories
Ask authors/readers for more resources
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 mu M. 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available