A New Nerve Growth Factor (ngf)-Mimetic Peptide Active On Neuropathic Pain In Rats(780 views) Colangelo AM, Bianco MR, Vitagliano L, Cavaliere C, Cirillo G, De Gioia L, Diana D, Colombo D, Redaelli C, Zaccaro L, Morelli G, Papa M, Sarmientos P, Alberghina L, Martegani E
Keywords: Bioactive Peptides, Gliosis, Neuropathic Pain, Nmr Structure, Agents Interacting With Transmitter, Hormone Or Drug Receptors, Brain Derived Neurotrophic Factor Receptor, Nerve Growth Factor Agonist, Protein L1l4, Protein Nl1l4, Protein Tyrosine Kinase A, Unclassified Drug, Amino Terminal Sequence, Animal Cell, Article, Cell Proliferation, Controlled Study, Fibroblast, Human, Human Cell, Nonhuman, Nuclear Magnetic Resonance, Peripheral Neuropathy, Priority Journal, Protein Phosphorylation, Protein Structure, Protein Synthesis, Biomimetic Materials, Cultured, Chick Embryo, Pain Measurement, Pc12 Cells, Peripheral Nervous System Diseases, Sprague-Dawley, Sciatic Neuropathy,
Affiliations: *** IBB - CNR ***
Laboratorio di Neuroscienze R. Levi-Montalcini, Dipartimento di Biotecnologie e Bioscienze, Universit di Milano-Bicocca, 20126 Milan, Italy
Laboratorio di Morfologia Delle Reti Neuronali, Dipartimento di Medicina Pubblica Clinica e Preventiva, Seconda Universit di Napoli, 80138 Naples, Italy
Centro Interuniversitario di Ricerca Sui Peptidi Bioattivi, Dipartimento Delle Scienze Biologiche, Consiglio Nazionale Delle Ricerche, 80138 Naples, Italy
Primm Srl, 20132 Milan, Italy
Primm Srl, Via Olgettina 58, 20132 Milan, Italy
References: Not available.
A New Nerve Growth Factor (ngf)-Mimetic Peptide Active On Neuropathic Pain In Rats
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 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. Copyright 2008 Society for Neuroscience
A New Nerve Growth Factor (ngf)-Mimetic Peptide Active On Neuropathic Pain In Rats