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Further evidence of NRF2s beneficial effects on ALS pathology were reported by clinical studies, which have shown that pharmacological activation of NRF2 improved the disease progression of ALS patients and reduced oxidative stress ( Collectively, these data show that the NRF2 pathway is dysfunctional in various neurodegenerative diseases and the effects of the reduced or lost activity of the NRF2-mediated antioxidant pathway in the brain are summarized in Figure 3

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Conversion of 4-hydroxyproline to oxalate begins with its oxidation to 1 -pyrroline-3-hydroxy-5-carboxylate by proline dehydrogenase 2 (encoded by the PRODH2 gene)