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Feiguin, F., Godena, V.K., Romano, G., D'Ambrogio, A., Klima, R., Baralle, F.E. (2009). Depletion of TDP-43 affects Drosophila motoneurons terminal synapsis and locomotive behavior.  FEBS Lett. 583(10): 1586--1592.
FlyBase ID
FBrf0208082
Publication Type
Research paper
Abstract

Pathological modifications in the highly conserved and ubiquitously expressed heterogeneous ribonucleoprotein TDP-43 were recently associated to neurodegenerative diseases including amyotrophic lateral sclerosis (ALS), a late-onset disorder that affects predominantly motoneurons [Neumann, M. et al. (2006) Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science 314, 130-133, Sreedharan, J. et al. (2008) TDP-43 mutations in familial and sporadic amyotrophic lateral sclerosis. Science 319, 1668-1672, Kabashi, E. et al. (2008) TARDBP mutations in individuals with sporadic and familial amyotrophic lateral sclerosis. Nat. Genet. 40, 572-574]. However, the function of TDP-43 in vivo is unknown and a possible direct role in neurodegeneration remains speculative. Here, we report that flies lacking Drosophila TDP-43 appeared externally normal but presented deficient locomotive behaviors, reduced life span and anatomical defects at the neuromuscular junctions. These phenotypes were rescued by expression of the human protein in a restricted group of neurons including motoneurons. Our results demonstrate the role of this protein in vivo and suggest an alternative explanation to ALS pathogenesis that may be more due to the lack of TDP 43 function than to the toxicity of the aggregates.

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    Language of Publication
    English
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    Parent Publication
    Publication Type
    Journal
    Abbreviation
    FEBS Lett.
    Title
    FEBS Letters
    Publication Year
    1968-
    ISBN/ISSN
    0014-5793
    Data From Reference
    Alleles (9)
    Genes (3)
    Human Disease Models (1)
    Natural transposons (1)
    Insertions (4)
    Experimental Tools (2)
    Transgenic Constructs (5)