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Mechanistically, metformin may activate Nrf2 through multiple pathways, including AMPK activation, inhibition of GSK-3mediated Nrf2 degradation, and modulation of intracellular redox homeostasis, all of which facilitate Nrf2 nuclear translocation and subsequent induction of downstream antioxidant genes 48,49

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PMID: 30126412

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Construct Validity The construct validity of disease models is determined by whether the etiology and pathogenesis leading to the disorder in the model correspond to those of the human disease