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


    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
    Issue number7
    Pages (from-to)2429-2434
    Number of pages6
    Publication statusPublished - 2009
    MoE publication typeA1 Journal article-refereed

    Cite this