FIGURE 2.

A model describing the copper transport system and its association with AD. Cu⁺ is taken up into brain cells by CTR1. DMT1 is involved in Cu²⁺ uptake. Accumulated Cu is sequestered into specific cellular locations by different Cu chaperones, such as CCS, COX17, and ATOX1. ATOX1 is suggested to transfer Cu⁺ to ATP7A and ATP7B, which help to import Cu⁺ into synaptic vesicles for release and/or directly mediate Cu export. Excessive intracellular Cu⁺ may activate the Fenton reaction to increase oxidative stress. Furthermore, Cu²⁺ is involved in the expression of the MMP responsible for the degradation of Aβ by activating the GSK3β pathway, which also contributes to tau hyper-phosphorylation. In the synaptic cleft, Cu binds to Aβ and facilitates the formation of senile plaques. CTR1, copper transporter 1; ATP7A, copper-transporting P-type ATPase; CCS, copper chaperone for superoxide dismutase; COX17, cytochrome oxidase enzyme complex; ATOX1, antioxidant protein-1; MMP, matrix metalloproteinases; GSK3β, glycogen synthase kinase 3β.