title: [C-terminal fragment of tetanus toxin: its use in neuronal network analysis and its potential as non-viral vector].
abstract: The atoxic C-terminal fragment of tetanus neurotoxin or TTC fragment presents similar retrograde and transsynaptic properties to that of holotoxin. Detection of this fragment is easier when it is associated with a fluorescent marker or with beta-galactosidase activity by genetic fusion or chemical conjugation. Thus, these tracers have been used to study and analyse the synaptic connections of a neural network. In this article, we shortly review the various methods used with this aim including: injection of the fusion protein, adenovirus in vivo expression and transgenesis. Since neural activity is essential for neuronal TTC binding and internalization, the functionality of connections can be also evaluated. Moreover, modifications of the retrograde transport can be detected by using this fragment. Thus, TTC fragment is an excellent tracer to analyse the connectivity and functionality of a neural network. The TTC fragment was also soon proposed as potential therapeutic vector to transport and to deliver a biological activity or gene in a neural network. With this aim, the efficiency of a translocation domain to induce the cytosolic release of the associated activity has been evaluated. The use of the TTC fragment to target specifically a neurotrophic factor to neurons and thus avoid secondary effects has been tested with interesting results.
authors.affiliation: Laboratoire de Neurobiologie Cellulaire et Moléculaire, Unité Propre de Recherche 9040, Centre National de la Recherche Scientifique, Institut Fédératif de Neurobiologie Alfred Fessard, 91198 Gif-sur-Yvette, France. sroux@nbcm.cnrc-gif.fr
authors.forename: Sylvie
authors.initials: S
authors.lastname: Roux
authors.forename: Cécile
authors.initials: C
authors.lastname: Saint Cloment
authors.forename: Thomas
authors.initials: T
authors.lastname: Curie
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Girard
authors.forename: Philippe
authors.initials: P
authors.lastname: Brûlet
authors.forename: Jordi
authors.initials: J
authors.lastname: Molgó
mesh_terms: D000818:Animals; D001370:Axonal Transport; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D009415:Nerve Net / Q000648:ultrastructure*; D009474:Neurons / Q000648:ultrastructure; D010446:Peptide Fragments / Q000235:genetics; D011993:Recombinant Fusion Proteins; D013569:Synapses / Q000648:ultrastructure; D013744:Tetanus Toxin / Q000235:genetics; D001616:beta-Galactosidase / Q000235:genetics
chemical_list: D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D013744:Tetanus Toxin; C040635:tetanus toxin fragment C; D049452:Green Fluorescent Proteins; D001616:beta-Galactosidase