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The Nrf2-Antioxidant Response Element Signaling Pathway and Its Activation by Oxidative Stress

However, research have been mainly focusing on APO E3 and E4 carriers, leaving open questions about the effect of APOE2 on insulin signaling

The direct influence of the E4 allele on FA-related bioenergetics (i.e., the transport and use of metabolites, in this case FAs, for energy) within the cerebrovasculature requires further attention, specifically in E4 carriers because of their increased cerebrovascular vulnerability observed with age which could impair nutrient transport to the brain and affect proper neuronal and glial functioning (Ojo et al., 2021)

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Previous studies considered carnitine as an active antioxidant, as carnitine ameliorated DPN by improving cellular energy metabolism by promoting long chain fatty acid -oxidation, stimulating glucose disposal and improving insulin resistance further by restoring Na+/K+-adenosine triphosphatase activity (26)