BenBedPhar will be present in the meeting of the international SFRR at Uruguay with a featured symposium on NRF2: https://sfrbm.org/meetings/sfrbm-sfrri-2023/featured-symposia/
You can find all the details of the symposium below:
‘Bench to Bedside Translation for Pharmacological Regulation of NRF2’
SfRBM – SFRRI 2023 SYMPOSIUM |Saturday, November 18, 2023 | Saturday, Session 1
Chairs: Giovanni E. Mann, PhD, King’s College London, UK and Henry J. Forman, University of Southern California, USA
Symposium Title: Bench to Bedside Translation for Pharmacological Regulation of NRF2
Symposia Summary: NRF2 (Nuclear factor erythroid 2-related factor 2) is a key transcription factor for regulation of cellular homeostatic. Its mode of action involves heterodimerization with other bZip transcription factors, of which the small MAF proteins F, G and K are the best characterized. The heterodimer activates the expression of genes that contain an Antioxidant Response Element (ARE), and these genes participate in protection against oxidative, inflammatory, metabolic or proteotoxic stress. Given the tremendous impact of this protein in physiology and pathology, it is not surprising that it has attracted a great deal of attention by the biomedical community. Moreover, contrary to most transcription factors, NRF2 is amenable to pharmacological activation by selectively inhibiting its degradation. The main repressor of NRF2 is the druggable E3 ligase adapter Kelch-likeECH-associated protein1 (KEAP1). Under unstressed conditions, KEAP1 targets NRF2 for Rbx1/Cullin 3-dependent ubiquitination and proteasomal degradation, but this repressor activity is blocked when specific cysteine residues in this protein are oxidized, or form adducts with electrophilic molecules. A much less explored mechanism of NRF2 repression is its glycogen synthase kinase (GSK-3)- mediated phosphorylation, which creates a phosphorylation-dependent site for interaction with the E3-ligase adapter β-transducin repeat-containing protein (β-TrCP). Binding of beta- TrCP to GSK-3- phosphorylated NRF2 leads to Rbx1/Cullin1-mediated ubiquitination and proteasomal degradation of NRF2. Therefore, KEAP1 and β-TrCP complement each other in NRF2 regulation under oxidative stress and cell signaling, respectively.
Proposed Speakers & Times:
10:45 pm – 11:15 am Development of Therapeutics to Target the “Dark Side” of NRF2 Donna Zhang, PhD, University of Arizona, USA
11:15 am – 11:45 am Activators and Inhibitors of NRF2 and their Potential for Clinical Translation
