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The Neh6 domain, which is a serine-rich region, contributes to regulate NRF2 stability and mediates the interaction with a third negative regulator, -transducin repeat-containing protein (-TrCP), through its DSGIS (Aspartic acid-Serine-Glycine-Isoleucine-Serine) and DSAPGS (Aspartic acid-Serine-Alanine-Proline-Glycine-Serine) motifs not recognized by KEAP1

Cytotoxicity assays, including MTT and SRB, showed significantly reduced toxicity for the PEGylated nanoparticle formulation compared to free tolcapone (cell viability exceeded 85% at 10, 25, and 50 M of the formula after 24 and 48 h of treatment)