Copper is one of the most abundant essential transition metals in the human body and is required for essential enzymes. It is involved in oxygen metabolism, collagen synthesis, skin pigmentation, the maintenance of vascular integrity, iron homeostasis, antioxidant defense, and neurotransmitter synthesis. It may also be involved in cellular signaling and may be involved in modulation of membrane receptor-ligand interactions, controlling the function of kinases and related phosphatases, and many cellular pathways. Its role is also important in the control of gene expression in the nucleus. Conversely, due to its redox activity, copper can also lead to the generation of toxic reactive oxygen species.

In the nervous system, copper is involved in the formation of myelin through the regulation of synaptic activity as well as excitatory cell death and neurotrophic factor-induced signaling cascades, and copper is important for various neuronal functions. In the brain, astrocytes are thought to be important regulators of copper homeostasis and may play a key role in copper metabolism in the brain due to their ability to efficiently take up, store, and export copper and even upregulate their copper storage capacity upon exposure to copper. Thus, this organ possesses sufficient mechanisms to regulate its copper metabolism. In the brain, impairment of the homeostatic mechanisms of copper metabolism in the brain has been associated with neurodegeneration in human diseases, and deficiencies of copper in the brain, such as Menkes disease and AD, and excesses of copper, such as Wilsons’ disease, have been associated with neurodegeneration.

In summary, cellular uptake, storage, and export of copper have to be tightly regulated to ensure sufficient copper supply for the synthesis of copper-containing enzymes but also to prevent copper-induced oxidative stress. A careful balance of control is important.

Scheiber, I. F., Mercer, J. F., & Dringen, R. (2014). Metabolism and functions of copper in brain. Progress in neurobiology, 116, 33–57. [Link]
Gromadzka, G., Tarnacka, B., Flaga, A., & Adamczyk, A. (2020). Copper Dyshomeostasis in Neurodegenerative Diseases-Therapeutic Implications. International journal of molecular sciences, 21(23), 9259. [Link]