Chronic oxidative stress impairs Nrf2 activation

In contrast to acute oxidative stress, Nrf2 becomes resistant to ROS during chronic oxidative stress in neurodegenerative disease, suggesting that activation of Nrf2 by a ROS-independent mechanism exists.

This is also confirmed in patients with diabetes who show increased oxidative stress causing cellular damage continues to occur despite the presence of Nrf2.

The issue then is how to activate ROS-resistant Nrf2 in patients with diabetes." (R1)

I will definitely read the referenced papers, maybe there is a way to restore normal function of Nrf2 after chronic exposure to OS.

References

1
Micronutrient-Induced Activation of Nrf2 and -Elevation of Intracellular Antioxidants for Reducing Oxidative Stress and Chronic Inflammation in Diabetes
2017