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Lipoic acid was found to upregulate the expression of -GCL and other antioxidant enzymes via the activation of the nuclear factor E2-related factor 2 (Nrf2)-dependent pathway (31, 33)

In both NAFLD mouse models and FFA-induced hepatocyte models, BMP4 upregulation enhances GPX4 expression at both the gene and protein levels, suggesting a protective role against ferroptosis

The high convergence of several important effects near one region where the R-domain, NBD1, R-insertion, and Lasso motif come together suggest the general importance of the R-domain interactions observed in our structures