PMID- 37840813
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231020
IS  - 2673-6217 (Electronic)
IS  - 2673-6217 (Print)
IS  - 2673-6217 (Linking)
VI  - 4
DP  - 2023
TI  - The untapped potential of targeting NRF2 in neurodegenerative disease.
PG  - 1270838
LID - 10.3389/fragi.2023.1270838 [doi]
LID - 1270838
AB  - Since its initial discovery almost three decades ago, the transcription factor 
      nuclear factor erythroid 2-related factor 2 (NRF2) has been shown to regulate a 
      host of downstream transcriptional responses and play a critical role in 
      preventing or promoting disease progression depending on the context. Critically, 
      while the importance of proper nuclear factor erythroid 2-related factor 2 
      function has been demonstrated across a variety of pathological settings, the 
      ability to progress NRF2-targeted therapeutics to clinic has remained 
      frustratingly elusive. This is particularly true in the case of age-related 
      pathologies, where nuclear factor erythroid 2-related factor 2 is a 
      well-established mitigator of many of the observed pathogenic effects, yet 
      options to target this pathway remain limited. Along these lines, loss of nuclear 
      factor erythroid 2-related factor 2 function has clearly been shown to enhance 
      neuropathological outcomes, with enhancing nuclear factor erythroid 2-related 
      factor 2 pathway activation to prevent neurodegenerative/neurological disease 
      progression continuing to be an active area of interest. One critical obstacle in 
      generating successful therapeutics for brain-related pathologies is the ability 
      of the compound to cross the blood brain barrier (BBB), which has also hampered 
      the implementation of several promising nuclear factor erythroid 2-related factor 
      2 inducers. Another limitation is that many nuclear factor erythroid 2-related 
      factor 2 activators have undesirable off-target effects due to their 
      electrophilic nature. Despite these constraints, the field has continued to 
      evolve, and several viable means of targeting nuclear factor erythroid 2-related 
      factor 2 in a neuropathological context have emerged. In this perspective, we 
      will briefly discuss the key findings and promising therapeutic options that have 
      been discovered to date, as well as highlight emerging areas of 
      NRF2-neurodegeneration research that provide hope for successfully targeting this 
      pathway in the future.
CI  - Copyright (c) 2023 Chen and Dodson.
FAU - Chen, Wei-Tai
AU  - Chen WT
AD  - Department of Pharmacology and Toxicology, College of Pharmacy, University of 
      Arizona, Tucson, AZ, United States.
FAU - Dodson, Matthew
AU  - Dodson M
AD  - Department of Pharmacology and Toxicology, College of Pharmacy, University of 
      Arizona, Tucson, AZ, United States.
LA  - eng
PT  - Journal Article
DEP - 20230928
PL  - Switzerland
TA  - Front Aging
JT  - Frontiers in aging
JID - 9918231199706676
PMC - PMC10569223
OTO - NOTNLM
OT  - KEAP1
OT  - Nrf2
OT  - neurodegeneration
OT  - oxidative stress
OT  - therapeutics
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2023/10/16 06:48
MHDA- 2023/10/16 06:49
PMCR- 2023/09/28
CRDT- 2023/10/16 04:22
PHST- 2023/08/01 00:00 [received]
PHST- 2023/09/18 00:00 [accepted]
PHST- 2023/10/16 06:49 [medline]
PHST- 2023/10/16 06:48 [pubmed]
PHST- 2023/10/16 04:22 [entrez]
PHST- 2023/09/28 00:00 [pmc-release]
AID - 1270838 [pii]
AID - 10.3389/fragi.2023.1270838 [doi]
PST - epublish
SO  - Front Aging. 2023 Sep 28;4:1270838. doi: 10.3389/fragi.2023.1270838. eCollection 
      2023.