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Neh4 and Neh5 are acidic conserved sequences that enhance the expression of Nrf2 target genes by binding cAMP responsive element binding protein ( As mentioned above, Nrf2 ubiquitinated by the Keap1-CUL3 complex under normal conditions is degraded by proteases in the cytoplasm

ACS Nano 14 , 1368113690 (2020)

This is a significant gap that complicates dosing optimization and raises questions about long-term effects that cannot be fully answered yet