The many “faces” of copper in medicine and treatment Original paper

What was studied?

This review explores the multifaceted roles of copper (Cu) in medicine, specifically its importance in human health, disease mechanisms, and its potential therapeutic applications. Copper is a vital micronutrient, serving as a cofactor for various enzymes involved in critical biological processes like oxidative stress, immune function, and cellular respiration. The study focuses on both copper deficiency and copper excess, highlighting the diseases that arise from imbalances in copper levels, such as Wilson’s disease and Menke’s disease, as well as the potential therapeutic uses of copper chelation in cancer, fibrosis, and neurodegenerative diseases. The review also addresses the role of copper in angiogenesis, oxidative stress, immune responses, and its involvement in diseases like Alzheimer’s and diabetes. Special attention is given to copper-requiring proteins, such as ceruloplasmin, cytochrome c oxidase, and superoxide dismutase, that depend on copper for their activity.

Who was studied?

The review covers several genetic disorders related to copper metabolism, including Wilson’s disease, Menke’s disease, and aceruloplasminemia, which result from mutations in copper transport and homeostasis genes like ATP7A and ATP7B. These conditions lead to either copper toxicity (in Wilson’s disease) or deficiency (in Menke’s disease and aceruloplasminemia), manifesting as various systemic effects such as neurological damage, liver dysfunction, and cardiovascular complications. The study also considers the role of copper in non-genetic diseases such as Alzheimer’s disease, diabetes, prion diseases, and cancer, where copper plays a dual role, either promoting or inhibiting disease progression depending on its concentration and the specific biological context. Additionally, the review investigates the impact of copper complexes in medical treatments and therapeutic interventions for these diseases.

Most important findings

Copper has a complex and dual role in human health. While copper deficiency leads to various health problems like impaired immune function, neurological deficits, and cardiovascular issues, copper excess, as seen in Wilson’s disease, results in toxic accumulation in tissues, particularly the liver and brain. The review also highlights the therapeutic potential of copper-lowering therapies in the treatment of conditions like cancer and fibrosis. Zinc therapy, commonly used in Wilson’s disease, works by competing with copper for absorption in the gastrointestinal tract, thus preventing copper buildup. The review also discusses ceruloplasmin (Cp) as a major copper-binding protein in the blood, playing an essential role in iron metabolism and preventing iron overload. Other copper-dependent proteins like cytochrome c oxidase, involved in mitochondrial energy production, and superoxide dismutase, which detoxifies reactive oxygen species (ROS), are also critical for maintaining cellular health.

Key implications

The findings of this review underscore the importance of copper regulation in maintaining health and preventing disease. Clinicians should be aware of the potential for copper toxicity in individuals with Wilson’s disease or those exposed to excess copper in the environment, such as in water or food sources. Copper chelation therapy could be a valuable tool in managing these conditions, especially in diseases like Wilson’s and in preventing copper-induced tumor progression. The role of copper in neurodegenerative diseases like Alzheimer’s, where it contributes to amyloid plaque formation, calls for further research into copper-modulating treatments. The dual role of copper in promoting and inhibiting disease progression suggests the need for careful monitoring of copper levels in patients with these conditions, alongside the use of targeted therapies that either promote or inhibit copper utilization.