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A scheme of biochemical defects of FRDA and how the activation of NRF2-signaling can rescue them.
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Description
FXN deficiency causes ATP synthesis reduction, and ROS production. High ROS levels decrease GPX4 expression and NRF2 nuclear translocation is hindered, impairing antioxidant defense. Nrf2 activators induce NRF2 phosphorylation, enhancing its nuclear translocation and promoting NRF2-target gene transcription, and GSH synthesis upregulation boosts GPX4 function, reducing ROS, iron accumulation, restoring FXN expression, and mitochondrial ATP production.
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