• Author: Jørgensen, Jesper Roland

    NsGene A/S, Ballerup

  • Author: Fransson, Anette

    Karolinska Institute

  • Author: Fjord-Larsen, Lone

    NsGene A/S, Ballerup

  • Author: Thompson, Lachlan H.

    University of Melbourne, Parkville, Florey Neuroscience Institute

  • Author: Houchins, Jeffrey P.

    R&D Systems Inc., Minneapolis

  • Author: Andrade, Nuno

    Lund University

  • Author: Torp, Malene

    NsGene A/S, Ballerup

  • Author: Kalkkinen, Nisse

    University of Helsinki, Helsinki, Protein Chemistry Research Group

  • Author: Andersson, Elisabet

    Karolinska Institute

  • Author: Lindvall, Olle

    Lund University

  • Author: Ulfendahl, Mats

    Karolinska Institute

  • Author: Brunak, Søren

    Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Kemitorvet, 2800, Kgs. Lyngby, Denmark

  • Author: Johansen, Teit E.

    NsGene A/S, Ballerup

  • Author: Wahlberg, Lars U.

    NsGene A/S, Ballerup

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Neurotrophic factors are secreted proteins responsible for migration, growth and survival of neurons during development, and for maintenance and plasticity of adult neurons. Here we present a novel secreted protein named Cometin which together with Meteorin defines a new evolutionary conserved protein family. During early mouse development, Cometin is found exclusively in the floor plate and from E13.5 also in dorsal root ganglions and inner ear but apparently not in the adult nervous system. In vitro, Cometin promotes neurite outgrowth from dorsal root ganglion cells which can be blocked by inhibition of the Janus or MEK kinases. In this assay, additive effects of Cometin and Meteorin are observed indicating separate receptors. Furthermore, Cometin supports migration of neuroblasts from subventricular zone explants to the same extend as stromal cell derived factor 1a. Given the neurotrophic properties in vitro, combined with the restricted inner ear expression during development, we further investigated Cometin in relation to deafness. In neomycin deafened guinea pigs, two weeks intracochlear infusion of recombinant Cometin supports spiral ganglion neuron survival and function. In contrast to the control group receiving artificial perilymph, Cometin treated animals retain normal electrically-evoked brainstem response which is maintained several weeks after treatment cessation. Neuroprotection is also evident from stereological analysis of the spiral ganglion. Altogether, these studies show that Cometin is a potent new neurotrophic factor with therapeutic potential.
Original languageEnglish
JournalExperimental Neurology
Publication date2012
Volume233
Issue1
Pages172-181
ISSN0014-4886
DOIs
StatePublished
CitationsWeb of Science® Times Cited: 3

Keywords

  • Floor plate, Meteorin, Novel protein, Trophic factor, Neurotrophic, Spiral ganglion, Migration
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