“…Unlike human F508del CFTR, ivacaftor does not potentiate mouse F508del cftr [ 20 ]. However, systemic ivacaftor treatment ameliorates hippocampal neuron atrophy in wildtype cftr in mice [ 19 ]. Furthermore, ivacaftor strongly promotes nuclear factor E2-related factor-2 (Nrf2) expression and nuclear translocation in mutated and wildtype human cystic fibrosis bronchial epithelial cells [ 21 ], which further promotes the translation of antioxidative gene elements, including NADPH oxidase 1 ( NOX1 ), quinone oxidoreductase 1 (NQO1), superoxide dismutase 2 ( SOD2 ), and heme oxygenase-1 ( HO1 ) [ 22 - 24 ].…”