title: A new nerve growth factor-mimetic peptide active on neuropathic pain in rats.
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. Two peptides named NL1L4 and L1L4 demonstrated good NGF agonist activity at a concentration as low as 3 mum. 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.affiliation: Laboratorio di Neuroscienze "R. Levi-Montalcini" and Dipartimento di Biotecnologie e Bioscienze, Università di Milano-Bicocca, 20126 Milan, Italy.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Colangelo
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Bianco
authors.forename: Luigi
authors.initials: L
authors.lastname: Vitagliano
authors.forename: Carlo
authors.initials: C
authors.lastname: Cavaliere
authors.forename: Giovanni
authors.initials: G
authors.lastname: Cirillo
authors.forename: Luca
authors.initials: L
authors.lastname: De Gioia
authors.forename: Donatella
authors.initials: D
authors.lastname: Diana
authors.forename: Daniele
authors.initials: D
authors.lastname: Colombo
authors.forename: Cristina
authors.initials: C
authors.lastname: Redaelli
authors.forename: Laura
authors.initials: L
authors.lastname: Zaccaro
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Morelli
authors.forename: Michele
authors.initials: M
authors.lastname: Papa
authors.forename: Paolo
authors.initials: P
authors.lastname: Sarmientos
authors.forename: Lilia
authors.initials: L
authors.lastname: Alberghina
authors.forename: Enzo
authors.initials: E
authors.lastname: Martegani
mesh_terms: D000818:Animals; D040761:Biomimetic Materials / Q000494:pharmacology / Q000627:therapeutic use*; D002478:Cells, Cultured; D002642:Chick Embryo; D006801:Humans; D008297:Male; D051379:Mice; D020932:Nerve Growth Factor / Q000819:agonists / Q000494:pharmacology / Q000627:therapeutic use*; D016716:PC12 Cells; D010146:Pain / Q000188:drug therapy* / Q000378:metabolism; D010147:Pain Measurement / Q000187:drug effects / Q000379:methods; D010455:Peptides / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use*; D010523:Peripheral Nervous System Diseases / Q000188:drug therapy* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020426:Sciatic Neuropathy / Q000188:drug therapy / Q000378:metabolism
chemical_list: D010455:Peptides; D020932:Nerve Growth Factor