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Other sources, such as monoamine oxidase (MAO) and nitric oxide synthase (NOS), contribute significant quantities of ROS, playing roles in various cellular physiopathological processes

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282 Copper ionophores are lipophilic molecules that reversibly bind copper and facilitate their transport across cellular membranes, including the plasma and mitochondrial membranes

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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