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It is possible that glutathione depletion by 0.5 mM DEM triggers de novo glutathione biosynthesis as a compensatory mechanism to replenish glutathione

Indeed, it is known that Nrf2 is a master factor for the regulation of antioxidant response elements (ARE) in several antioxidant and phase II detoxifying proteins in different cell types, including nerve cells (Kobayashi and Yamamoto, 2013), and several reports have shown that although DHA itself does not bind Nrf2, it may stimulate transcriptional activity of ARE-containing genes through activation of Nrf2 upon generation of 4-hydroxy-2-hexenal, which indeed activates Nrf2 (Ishikado et al., 2013)

Notably, recombinant expression of WT FSP1 protein displayed a yellow hue, indicative of bound FAD, whereas the D285N mutant protein was white, consistent with a loss of FAD binding (Extended Data Fig

However, this research is subject to certain limitations

Stemler, K

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