title: An in vitro study of peptide-loaded alginate nanospheres for antagonizing the inhibitory effect of Nogo-A protein on axonal growth.
abstract: The adult mammalian central nervous system has limited ability to regenerate after injury. This is due, in part, to the presence of myelin-associated axon growth inhibitory proteins such as Nogo-A that bind and activate the Nogo receptor, leading to profound inhibition of actin-based motility within the growing axon tip. This paper presents an in vitro study of the use of a Nogo receptor-blocking peptide to antagonize the inhibitory effect of Nogo-A on axon growth. Alginate nanospheres were fabricated using an emulsion technique and loaded with Nogo receptor-blocking peptide, or with other model proteins. Protein release profiles were studied, and retention of the bioactivity of released proteins was verified. Primary dorsal root ganglion neurons were cultured and their ability to grow neurites was challenged with Nogo-A chimeric protein in the absence or presence of Nogo receptor antagonist peptide-loaded alginate nanospheres. Our results demonstrate that peptide released from alginate nanospheres could overcome the growth inhibitory effect of Nogo-A, suggesting that a similar peptide delivery strategy using alginate nanospheres might be used to improve axon regeneration within the injured central nervous system.
authors.affiliation: Division of Biomedical Engineering, University of Saskatchewan, Saskatoon SK S7N 5A9, Canada.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhai
authors.forename: X B
authors.initials: XB
authors.lastname: Chen
authors.forename: David J
authors.initials: DJ
authors.lastname: Schreyer
mesh_terms: D000464:Alginates / Q000737:chemistry*; D000818:Animals; D001369:Axons / Q000000981:diagnostic imaging / Q000187:drug effects / Q000502:physiology*; D049108:Cell Enlargement / Q000187:drug effects; D002478:Cells, Cultured; D004058:Diffusion; D004347:Drug Interactions; D005727:Ganglia, Spinal / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D008297:Male; D009185:Myelin Proteins / Q000008:administration & dosage*; D053769:Nanocapsules / Q000737:chemistry* / Q000648:ultrastructure; D054118:Nanospheres / Q000737:chemistry / Q000648:ultrastructure; D009416:Nerve Regeneration / Q000187:drug effects / Q000502:physiology*; D000070798:Nogo Proteins; D010455:Peptides / Q000008:administration & dosage* / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D014463:Ultrasonography
chemical_list: D000464:Alginates; D006603:Hexuronic Acids; D009185:Myelin Proteins; D053769:Nanocapsules; D000070798:Nogo Proteins; D010455:Peptides; C000603197:Rtn4 protein, rat; D020723:Glucuronic Acid