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Although SOD-based approaches are attractive because of their direct ROS-scavenging activity, their development has been restricted by poor oral bioavailability, unfavorable pharmacokinetics, and limited stability ( in vivo persistence ( These limitations have shifted attention toward strategies that do not rely solely on exogenous radical scavengers, but instead enhance endogenous cytoprotective programs or improve delivery to diseased tissue ( 4.3 Novel therapeutic strategies targeting the NRF2 pathway 4.3.1 The NRF2 pathway Several studies have reported dysregulation of the transcription factor NRF2, a master regulator of cellular redox homeostasis, in patients with MS and in EAE mice model (van Horssen et al., 2010