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Proc Natl Acad Sci U S A. 2009 Feb 17;106(7):2429-34. doi: 10.1073/pnas.0810996106. Epub 2009 Jan 22.

Evidence that DmMANF is an invertebrate neurotrophic factor supporting dopaminergic neurons.

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1
Institute of Biotechnology, University of Helsinki, 00014, Helsinki, Finland.

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.

PMID:
19164766
PMCID:
PMC2650173
DOI:
10.1073/pnas.0810996106
[Indexed for MEDLINE]
Free PMC Article
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