Targeting the NRF2 pathway for disease modification in neurodegenerative diseases: mechanisms and therapeutic implications

Abstract

NRF2 constitutes a central regulator of cellular defense mechanisms, including antioxidant, anti-inflammatory and mitochondrial pathways, making it highly attractive for disease modification in neurodegenerative disorders.

Key Findings

• NRF2 is central regulator of antioxidant, anti-inflammatory, and mitochondrial pathways
• NRF2 dysfunction observed in AD, PD, MS, and ALS
• Dimethyl fumarate approved for MS also shows benefits in AD, PD, ALS models
• Omaveloxolone gained FDA approval (2023) for Friedreich's ataxia via NRF2 activation
• BACH1 inhibitors represent next-generation NRF2 activation strategies

Clinical Significance

Citation

Mayer, C. et al. (2024). NRF2 in neurodegenerative diseases. Frontiers in Pharmacology.