This Session, "Nrf2 Signaling Pathways in Model Systems: A Master Regulator of Neurotoxicity and a Potential Therapeutic Target," was chaired by Dr. Richard Nass of the Indiana University School of Medicine, and Dr. Jeffrey Johnson of the University of Wisconsin Madison. The symposium highlighted Nrf2 dynamics in a variety of model organisms, including nematodes, flies, zebrafish, rodents, and humans.
Nrf2 is a transcription factor involved in the endogenous antioxidant response of organisms. Nrf2 is maintained in the cytosol of cells, bound to Keap-1, until cellular stress responses trigger its release and translocation into the nucleus. The targets of Nrf2 are important for maintaining or restoring glutathione concentrations and redox balance, and contribute to phase II metabolism. A variety of traditional and modern dietary and pharmacological agents have been deemed as potent “antioxidants” because they contain compounds known to induce Nrf2 and the antioxidant response, such as cruciferous vegetables and spices. Though these compounds have been suggested to have numerous health benefits, this symposium investigated the role of Nrf2 signaling as a moderator of neurotoxicity.
Dr. Richard Nass discussed the role of SKN-1, a homolog of Nrf2 in the nematode, is important in the mediation of methylmercury-induced neurodegeneration resulting from neurotoxicity and oxidative stress.
Dr. Dirk Bohmann of the University of Rochester Medical Center presented his research studying the Nrf2 homolog CncC in flies. He explained that as organisms age, it becomes more difficult to turn stimuli responses on and off. Small Maf proteins may be crucial to maintain the sensitivity of these responses.
Dr. Evan Gallagher of the University of Washington discussed Nrf2 signaling in zebrafish in the etiology of olfactory epithelial injury, cell death, and olfactory neurobehavioral injury from cadmium toxicity.
Dr. Jeffrey Johnson presented his research regarding the attenuation or remediation of induced murine brain lesions through Nrf2 activation, and in the clearance or inhibition of protein aggregation in the development of neurodegenerative disease.
Dr. Donna Zhang of the University of Arizona discussed the role of the Nrf2 antioxidant response in the attenuation of liver and lung pathologies, and addressed the non-canonical mechanism of Nrf2 induction via p62 and Keap1 colocalization.
Ultimately, this symposium underscored the importance of Nrf2 signaling and the antioxidant response in the prevention and remediation of disease. Though factors such as environmental contamination and aging may contribute to the development of neurological disease or neurodegeneration, the increased public attention to antioxidant consumption of Nrf2 inducers in diet may aid in the prevention of neurodegenerative or neurobehavioral diseases.
This blog discusses highlights from the SOT Annual Meeting and ToxExpo Symposium Session, "Nrf2 Signaling Pathways in Model Systems: A Master Regulator of Neurotoxicity and a Potential Therapeutic Target."