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(2) the upregulation of drug efflux pumps (e.g., MRP1-2), which can actively pump ATO and its metabolites out of the cell, reducing intracellular accumulation

KD of HACE1 , which encodes an E3 ubiquitin-ligase involved in the UPS, was shown to exacerbate LPS-induced inflammation in BV2 microglia [237]

The mechanism may be that copper deficiency affects brain functioning by impairing brain mitochondrial function to damage energy metabolism (Munakata et al., 2005)