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Nrf2 Modulation by Natural Compounds in Aging, Neurodegeneration, and Neuropathic Pain.
Jurga Bernatoniene1,2, Dalia M Kopustinskiene2, Roberto Casale3
1Department of Drug Technology and Social Pharmacy, Faculty of Pharmacy, Medical Academy, Lithuanian University of Health Sciences, Sukileliu Pr. 13, LT-50161 Kaunas, Lithuania.
Pharmaceutics
|January 28, 2026
Summary
Nuclear factor erythroid 2-related factor 2 (Nrf2) links aging, neurodegeneration, and neuropathic pain by regulating cellular defense. Modulating Nrf2 offers a promising therapeutic strategy for these conditions.
Area of Science:
- Cellular Biology
- Neuroscience
- Aging Research
Background:
- Aging is associated with increased oxidative stress, inflammation, and reduced Nrf2 activity, heightening disease susceptibility.
- Impaired Nrf2 signaling is implicated in the pathogenesis of neurodegenerative diseases like Alzheimer's, Parkinson's, Huntington's, and ALS.
- Similar mechanisms involving Nrf2 dysfunction are observed in neuropathic pain.
Purpose of the Study:
- To review the multifaceted role of Nrf2 in aging, neurodegeneration, and neuropathic pain.
- To explore natural compounds as Nrf2 modulators and discuss their therapeutic potential.
- To identify challenges and future directions for Nrf2-targeted therapies.
Main Methods:
- Literature review of studies investigating Nrf2 pathways in aging and neurological disorders.
- Analysis of natural compounds targeting Nrf2, including flavonoids, polyphenols, terpenoids, and alkaloids.
- Evaluation of translational challenges and potential solutions for Nrf2-based therapeutics.
Main Results:
- Nrf2 activity declines with age, contributing to oxidative stress and inflammation.
- Dysfunctional Nrf2 signaling exacerbates neuroinflammation, oxidative damage, and mitochondrial dysfunction in neurodegenerative diseases.
- Nrf2 modulation shows potential as an analgesic strategy for neuropathic pain.
Conclusions:
- Nrf2 is a pivotal regulator connecting aging, neurodegeneration, and neuropathic pain.
- Natural Nrf2 modulators offer therapeutic promise but face significant translational hurdles.
- Future research should focus on optimizing delivery, addressing genetic variations, and establishing safety and efficacy for Nrf2-targeted interventions.
Keywords:
Nrf2 modulatorsagingnatural compoundsneuroinflammationnuclear factor erythroid 2–related factor 2 (Nrf2)oxidative stressMore Related Videos
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