Evidence that DmMANF is an invertebrate neurotrophic factor supporting dopaminergic neurons

Mari Palgi, Riitta Lindström, Johan Peränen, Petteri Piepponen, Mart Saarma, Tapio I Heino

    Research output: Contribution to journalArticleScientificpeer-review

    Abstract

    In vertebrates the development and function of the nervous system is regulated by neurotrophic factors (NTFs). Despite extensive searches no neurotrophic factors have been found in invertebrates. However, cell ablation studies in Drosophila suggest trophic interaction between neurons and glia. Here we report the invertebrate neurotrophic factor in Drosophila, DmMANF, homologous to mammalian MANF and CDNF. DmMANF is expressed in glia and essential for maintenance of dopamine positive neurites and dopamine levels. The abolishment of both maternal and zygotic DmMANF leads to the degeneration of axonal bundles in the embryonic central nervous system and subsequent nonapoptotic cell death. The rescue experiments confirm DmMANF as a functional ortholog of the human MANF gene thus opening the window for comparative studies of this protein family with potential for the treatment of Parkinson's disease.
    Original languageEnglish
    JournalProceedings of the National Academy of Sciences of the United States of America
    Volume106
    Issue number7
    Pages (from-to)2429-2434
    Number of pages6
    ISSN0027-8424
    DOIs
    Publication statusPublished - 2009
    MoE publication typeA1 Journal article-refereed

    Cite this

    @article{50f3ce00ac96467e933643cc77ba0e36,
    title = "Evidence that DmMANF is an invertebrate neurotrophic factor supporting dopaminergic neurons",
    abstract = "In vertebrates the development and function of the nervous system is regulated by neurotrophic factors (NTFs). Despite extensive searches no neurotrophic factors have been found in invertebrates. However, cell ablation studies in Drosophila suggest trophic interaction between neurons and glia. Here we report the invertebrate neurotrophic factor in Drosophila, DmMANF, homologous to mammalian MANF and CDNF. DmMANF is expressed in glia and essential for maintenance of dopamine positive neurites and dopamine levels. The abolishment of both maternal and zygotic DmMANF leads to the degeneration of axonal bundles in the embryonic central nervous system and subsequent nonapoptotic cell death. The rescue experiments confirm DmMANF as a functional ortholog of the human MANF gene thus opening the window for comparative studies of this protein family with potential for the treatment of Parkinson's disease.",
    author = "Mari Palgi and Riitta Lindstr{\"o}m and Johan Per{\"a}nen and Petteri Piepponen and Mart Saarma and Heino, {Tapio I}",
    year = "2009",
    doi = "10.1073/pnas.0810996106",
    language = "English",
    volume = "106",
    pages = "2429--2434",
    journal = "Proceedings of the National Academy of Sciences of the United States of America",
    issn = "0027-8424",
    publisher = "National Academy of Sciences",
    number = "7",

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    Evidence that DmMANF is an invertebrate neurotrophic factor supporting dopaminergic neurons. / Palgi, Mari; Lindström, Riitta; Peränen, Johan; Piepponen, Petteri; Saarma, Mart; Heino, Tapio I.

    In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 106, No. 7, 2009, p. 2429-2434.

    Research output: Contribution to journalArticleScientificpeer-review

    TY - JOUR

    T1 - Evidence that DmMANF is an invertebrate neurotrophic factor supporting dopaminergic neurons

    AU - Palgi, Mari

    AU - Lindström, Riitta

    AU - Peränen, Johan

    AU - Piepponen, Petteri

    AU - Saarma, Mart

    AU - Heino, Tapio I

    PY - 2009

    Y1 - 2009

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    AB - In vertebrates the development and function of the nervous system is regulated by neurotrophic factors (NTFs). Despite extensive searches no neurotrophic factors have been found in invertebrates. However, cell ablation studies in Drosophila suggest trophic interaction between neurons and glia. Here we report the invertebrate neurotrophic factor in Drosophila, DmMANF, homologous to mammalian MANF and CDNF. DmMANF is expressed in glia and essential for maintenance of dopamine positive neurites and dopamine levels. The abolishment of both maternal and zygotic DmMANF leads to the degeneration of axonal bundles in the embryonic central nervous system and subsequent nonapoptotic cell death. The rescue experiments confirm DmMANF as a functional ortholog of the human MANF gene thus opening the window for comparative studies of this protein family with potential for the treatment of Parkinson's disease.

    U2 - 10.1073/pnas.0810996106

    DO - 10.1073/pnas.0810996106

    M3 - Article

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    JO - Proceedings of the National Academy of Sciences of the United States of America

    JF - Proceedings of the National Academy of Sciences of the United States of America

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    ER -