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NF-kappa B disinhibition contributes to dendrite defects in fly models of neurodegenerative diseases

Title
NF-kappa B disinhibition contributes to dendrite defects in fly models of neurodegenerative diseases
Authors
Han, Myeong HoonKwon, Min JeeKo, Byung SuHyeon, Do YoungLee, DavinKim, Hyung-JunHwang, DaeheeLee, Sung Bae
DGIST Authors
Lee, Sung Bae
Issue Date
2020-12
Citation
Journal of Cell Biology, 219(12), e202004107
Type
Article
Article Type
Article
Keywords
AMYOTROPHIC-LATERAL-SCLEROSISNUCLEAR TRANSLOCATIONFACTOR RELISHC-RELTRANSCRIPTIONACTIVATIONDROSOPHILANEUROINFLAMMATIONNEURONSPATHWAY
ISSN
0021-9525
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. © 2020 Han et al.
URI
http://hdl.handle.net/20.500.11750/12519
DOI
10.1083/jcb.202004107
Publisher
Rockefeller University Press
Related Researcher
  • Author Lee, Sung Bae Laboratory of Neurodegenerative Diseases and Aging
  • Research Interests Cellular mechanism of neurodegenerative diseases; Neuronal maintenance and remodeling; 퇴행성 뇌질환의 세포기전; 신경계 유지 및 리모델링 연구
Files:
Collection:
Department of Brain and Cognitive SciencesLaboratory of Neurodegenerative Diseases and Aging1. Journal Articles


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