A newly emerging player is a nuclear inhibitor of Nrf2, BTB domain and CNC homolog 1 (Bach1). Hence, the hope in therapeutics is now linked to the FDA approved dimethylfumarate, whose derivative, monomethylfumarate, as we demonstrated recently, is much less toxic but equally biologically potent and an ideal candidate for clinical trials right now. At this point, no displacement activators exhibit sufficient biological activity in comparison with common Nrf2 activators working via Keap1 thiol modification. There are two opposite “chemical” mechanisms underlying such activation: the first one is a non-specific covalent modification of Keap1 thiols, resulting in side effects of varied severity, and the second one is the shift of the Nrf2-Kelch-like ECH associated protein-1 (Keap1) binding equilibrium in the presence of a competitive and chemically benign displacement agent. This mini-review presents the authors' vision on the current status and future trends in the development of neuroprotective agents working via activation of nuclear factor erythroid 2-related factor 2 (Nrf2), and in particular, via disruption of Nrf2-Keap1 interaction. Ion for Parkinson’s disease to IGG., Conflict of Interest: None Parkinson, National Parkinson Foundation (CSRA chapter) to BT and Winifred Masterson Burke Foundation, and Thomas Hartman Foundat Source of Support: This work is supported in part by grants from NIH NS062165, NS060885, Michael J Fox Foundation for Parkinson’s Research, Parfore 2ġ Department of Cell Biology and Anatomy, School of Medicine, New York Medical College, Valhalla, NY Department of Chemistry and Physical Sciences, Dyson College, Pace University, Pleasantville, NY, USA 2 Departments of Pharmacology, Toxicology and Neurology, Medical College of Georgia, Augusta University, Augusta, GA, USA Date of Acceptanceĭepartments of Pharmacology, Toxicology and Neurology, Medical College of Georgia, Augusta University, Augusta, GAĭepartment of Cell Biology and Anatomy, School of Medicine, New York Medical College, Valhalla, NY Department of Chemistry and Physical Sciences, Dyson College, Pace University, Pleasantville, NY The status of Nrf2-based therapeutics: current perspectives and future prospects