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In brain tissue, misfolded proteins such as amyloid-beta and tau can sequester copper ions, creating local copper deficiency while simultaneously generating reactive oxygen species through aberrant metal-protein interactions

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This stress leads to suppression of forkhead box O1 (FoxO1) signaling and subsequent upregulation of thioredoxin interacting protein, inhibition of insulin and SOD-2 expression, re-expression of Neurog3, and -cell dedifferentiation and functional failure