Transcriptomics

Dataset Information

0

Anakinra restores cellular proteostasis by coupling mitochondrial redox balance to autophagy


ABSTRACT: Autophagy selectively degrades aggregation-prone misfolded proteins caused by defective cellular proteostasis. However, the complexity of autophagy may prevent the full appreciation of how its modulation could be used as a therapeutic strategy in disease management. Here we define a molecular pathway through which recombinant interleukin-1 receptor antagonist (IL-1Ra, anakinra) affects cellular proteostasis independently from the IL-1 receptor (IL-1R1). Anakinra promoted H2O2-driven autophagy through a xenobiotic sensing pathway involving the aryl hydrocarbon receptor that, activated through the indoleamine 2,3-dioxygenase 1-kynurenine pathway, transcriptionally activates NADPH Oxidase 4 independent of the IL-1R1. By coupling the mitochondrial redox balance to autophagy, anakinra improved the dysregulated proteostasis network in murine and human cystic fibrosis. We anticipate that anakinra may represent a therapeutic option in addition to its IL-1R1 dependent anti-inflammatory properties by acting at the intersection of mitochondrial oxidative stress and autophagy with the capacity to restore conditions in which defective proteostasis leads to human disease.

ORGANISM(S): Mus musculus

PROVIDER: GSE188809 | GEO | 2021/11/27

REPOSITORIES: GEO

Dataset's files

Source:
Action DRS
Other
Items per page:
1 - 1 of 1

Similar Datasets

| PRJNA780423 | ENA
2009-12-31 | GSE17590 | GEO
2013-12-10 | E-MTAB-1567 | biostudies-arrayexpress
2023-10-04 | GSE236606 | GEO
2006-03-25 | GSE4507 | GEO
2020-04-24 | GSE149195 | GEO
2023-10-04 | GSE236552 | GEO
2022-08-05 | GSE180339 | GEO
2020-03-19 | GSE132781 | GEO
2021-07-28 | GSE174638 | GEO