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Citation
Feuillette, S., Charbonnier, C., Frebourg, T., Campion, D., Lecourtois, M. (2020). A Connected Network of Interacting Proteins Is Involved in Human-Tau Toxicity in Drosophila.  Front. Neurosci. 14(): 68.
FlyBase ID
FBrf0244983
Publication Type
Research paper
Abstract

Tauopathies are neurodegenerative diseases characterized by the presence of aggregates of abnormally phosphorylated Tau. Deciphering the pathophysiological mechanisms that lead from the alteration of Tau biology to neuronal death depends on the identification of Tau cellular partners. Combining genetic and transcriptomic analyses in Drosophila, we identified 77 new modulators of human Tau-induced toxicity, bringing to 301 the number of Tau genetic interactors identified so far in flies. Network analysis showed that 229 of these genetic modulators constitute a connected network. The addition of 77 new genes strengthened the network structure, increased the intergenic connectivity and brought up key hubs with high connectivities, namely Src64B/FYN, Src42A/FRK, kuz/ADAM10, heph/PTBP1, scrib/SCRIB, and Cam/CALM3. Interestingly, we established for the first time a genetic link between Tau-induced toxicity and ADAM10, a recognized Alzheimer Disease protective factor. In addition, our data support the importance of the presynaptic compartment in mediating Tau toxicity.

PubMed ID
PubMed Central ID
PMC7026268 (PMC) (EuropePMC)
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    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Front. Neurosci.
    Title
    Frontiers in neuroscience
    ISBN/ISSN
    1662-453X 1662-4548
    Data From Reference
    Alleles (126)
    Genes (79)
    Human Disease Models (1)
    Insertions (6)
    Transgenic Constructs (50)