Nrf2/Keap1/ARE signaling: Towards specific regulation.
Life Sci
; 291: 120111, 2022 Feb 15.
Article
in English
| MEDLINE | ID: covidwho-1487890
ABSTRACT
The Nrf2 transcription factor governs the expression of hundreds genes involved in cell defense against oxidative stress, the hallmark of numerous diseases such as neurodegenerative, cardiovascular, some viral pathologies, diabetes and others. The main route for Nrf2 activity regulation is via interactions with the Keap1 protein. Under the normoxia the Keap1 binds the Nrf2 and targets it to the proteasomal degradation, while the Keap1 is regenerated. Upon oxidative stress the interactions between Nrf2 and Keap1 are interrupted and the Nrf2 activates the transcription of the protective genes. Currently, the Nrf2 system activation is considered as a powerful cytoprotective strategy for treatment of different pathologies, which pathogenesis relies on oxidative stress including viral diseases of pivotal importance such as COVID-19. The implementation of this strategy is accomplished mainly through the inactivation of the Keap1 "guardian" function. Two approaches are now developing the Keap1 modification via electrophilic agents, which leads to the Nrf2 release, and direct interruption of the Nrf2Keap1 protein-protein interactions (PPI). Because of theirs chemical structure, the Nrf2 electrophilic inducers could non-specifically interact with others cellular proteins leading to undesired effects. Whereas the non-electrophilic inhibitors of the Nrf2Keap1 PPI could be more specific, thereby widening the therapeutic window.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Oxidative Stress
/
NF-E2-Related Factor 2
/
Molecular Targeted Therapy
/
Antioxidant Response Elements
/
Kelch-Like ECH-Associated Protein 1
Limits:
Animals
/
Humans
Language:
English
Journal:
Life Sci
Year:
2022
Document Type:
Article
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