Open Close
Reference
Citation
Han, M.H., Kwon, M.J., Ko, B.S., Hyeon, D.Y., Lee, D., Kim, H.J., Hwang, D., Lee, S.B. (2020). NF-κB disinhibition contributes to dendrite defects in fly models of neurodegenerative diseases.  J. Cell Biol. 219(12): e202004107.
FlyBase ID
FBrf0247016
Publication Type
Research paper
Abstract

Dendrite pathology is frequently observed in various neurodegenerative diseases (NDs). Although previous studies identified several pathogenic mediators of dendrite defects that act through loss of function in NDs, the underlying pathogenic mechanisms remain largely unexplored. Here, our search for additional pathogenic contributors to dendrite defects in NDs identifies Relish/NF-κB as a novel gain-of-toxicity-based mediator of dendrite defects in animal models for polyglutamine (polyQ) diseases and amyotrophic lateral sclerosis (ALS). In a Drosophila model for polyQ diseases, polyQ-induced dendrite defects require Dredd/Caspase-8-mediated endoproteolytic cleavage of Relish to generate the N-terminal fragment, Rel68, and subsequent Charon-mediated nuclear localization of Rel68. Rel68 alone induced neuronal toxicity causing dendrite and behavioral defects, and we identify two novel transcriptional targets, Tup and Pros, that mediate Rel68-induced neuronal toxicity. Finally, we show that Rel68-induced toxicity also contributes to dendrite and behavioral defects in a Drosophila model for ALS. Collectively, our data propose disinhibition of latent toxicity of Relish/NF-κB as a novel pathogenic mechanism underlying dendrite pathology in NDs.

PubMed ID
PubMed Central ID
PMC7588142 (PMC) (EuropePMC)
Associated Information
Comments
Associated Files
Other Information
Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    J. Cell Biol.
    Title
    Journal of Cell Biology
    Publication Year
    1966-
    ISBN/ISSN
    0021-9525
    Data From Reference
    Alleles (43)
    Genes (34)
    Human Disease Models (3)
    Natural transposons (1)
    Insertions (1)
    Experimental Tools (4)
    Transgenic Constructs (42)