PMID- 37470218
OWN - NLM
STAT- MEDLINE
DCOM- 20240408
LR  - 20240410
IS  - 1557-7716 (Electronic)
IS  - 1523-0864 (Linking)
VI  - 40
IP  - 10-12
DP  - 2024 Apr
TI  - Modulation of NRF2: Biological Dualism in Cancer, Targets and Possible 
      Therapeutic Applications.
PG  - 636-662
LID - 10.1089/ars.2022.0213 [doi]
AB  - Significance: The nuclear factor erythroid 2-related factor 2 (NRF2)-Kelch-like 
      ECH-associated protein 1 (KEAP1) system is a master regulator of redox 
      homeostasis and cell adaptation to a variety of exogenous and endogenous 
      stressors. Accumulating evidence from the last decade indicates that the 
      impairment of the redox balance leads to oxidative stress (OS), a common 
      alteration occurring in many human acute and chronic inflammatory diseases, such 
      as cancer, diabetes, neurodegeneration, and metabolic disorders, and aging. 
      Recent Advances: Being located at the intersection of crucial signaling pathways, 
      NRF2 can influence several cellular functions, which extend beyond the 
      maintenance of the redox balance and include cellular metabolism, proteostasis, 
      mitochondrial function and inflammation. For this reason, there is a growing 
      interest in the pharmacologic manipulation of NRF2 for therapeutic purposes, 
      which requires the accurate knowledge of the cell context and the specific time 
      frame both of NRF2 activation and inhibition. This appears to be an important 
      prerequisite and reflects the extreme complexity of the NRF2 signaling, 
      characterized by an intrinsic dualism that mediates beneficial or detrimental 
      effects even in the same biological process. Critical Issues: Of crucial 
      importance will be to understand whether the NRF2 activity modulation might be 
      exploited to exert beneficial outcomes in patients suffering from pathological 
      conditions, in which the OS and the deregulation of inflammatory processes play a 
      crucial role. Future Directions: In this review, we discuss the dual involvement 
      of NRF2 in aging, neurodegeneration, metabolic diseases, long-COVID-19, and 
      carcinogenesis and we present an overview of the most recent therapeutic 
      modulators of NRF2, particularly emphasizing on those selected for clinical 
      trials. Antioxid. Redox Signal. 40, 636-662.
FAU - Gallorini, Marialucia
AU  - Gallorini M
AD  - Department of Pharmacy, University "G. d'Annunzio" Chieti-Pescara, Chieti, Italy.
FAU - Carradori, Simone
AU  - Carradori S
AUID- ORCID: 0000-0002-8698-9440
AD  - Department of Pharmacy, University "G. d'Annunzio" Chieti-Pescara, Chieti, Italy.
FAU - Panieri, Emiliano
AU  - Panieri E
AUID- ORCID: 0000-0001-7989-7145
AD  - Department of Physiology and Pharmacology "Vittorio Erspamer," Sapienza 
      University of Rome, Rome, Italy.
AD  - Department of General Direction (DG), Section of Hazardous Substances, 
      Environmental Education and Training for the Technical Coordination of Management 
      Activities (DGTEC), Italian Institute for Environmental Protection and Research, 
      Rome, Italy.
FAU - Sova, Matej
AU  - Sova M
AD  - Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of 
      Ljubljana, Ljubljana, Slovenia.
FAU - Saso, Luciano
AU  - Saso L
AD  - Department of Physiology and Pharmacology "Vittorio Erspamer," Sapienza 
      University of Rome, Rome, Italy.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20230906
PL  - United States
TA  - Antioxid Redox Signal
JT  - Antioxidants & redox signaling
JID - 100888899
RN  - 0 (Kelch-Like ECH-Associated Protein 1)
RN  - 0 (NF-E2-Related Factor 2)
SB  - IM
MH  - Humans
MH  - Kelch-Like ECH-Associated Protein 1/metabolism
MH  - *Neoplasms/drug therapy
MH  - *NF-E2-Related Factor 2/metabolism
MH  - Oxidative Stress/physiology
MH  - Post-Acute COVID-19 Syndrome
OTO - NOTNLM
OT  - NRF2
OT  - activation
OT  - cancer
OT  - inflammation
OT  - inhibition
OT  - modulation
OT  - oxidative stress
OT  - therapy
EDAT- 2023/07/20 06:42
MHDA- 2024/04/08 06:42
CRDT- 2023/07/20 05:43
PHST- 2024/04/08 06:42 [medline]
PHST- 2023/07/20 06:42 [pubmed]
PHST- 2023/07/20 05:43 [entrez]
AID - 10.1089/ars.2022.0213 [doi]
PST - ppublish
SO  - Antioxid Redox Signal. 2024 Apr;40(10-12):636-662. doi: 10.1089/ars.2022.0213. 
      Epub 2023 Sep 6.