Emerging Roles of Metallothioneins in Human Pathophysiology: A Review

Background

Metallothioneins (MTs) are small molecular-weight proteins that either bind or release essential transition metals, depending on a specific cell situation. There are 4 major isoforms of MTs (1–4), of which MT1/2 is found in every cell in the body.

Aim

To provide a comprehensive discussion on the role of metallothionein in human pathophysiology.

Methods

This review was conducted using a variety of search engines, including Google Scholar, PubMed Central, Scopus, Web of Science, and others.

Results

The antioxidant property of MT is enhanced based on the availability of zinc. MTs reduce Pro-inflammatory cytokine production and shift the Th17/Treg balance, ultimately alleviating inflammatory diseases. In neurodegenerative diseases, MTs interact with protein aggregates and modulate their formation and toxicity. The MT's molecular processes in neurodegenerative illnesses include metal ion control, antioxidant activity, and anti-inflammatory actions. In cancer, MT acts as a tumor suppressor in the early stages and promotes tumor progression in the later stages. Only a few MT isoform-targeting approaches have been approved for use as therapeutic drugs.

Conclusion

Metallothioneins play vital roles in controlling oxidative stress, immunity, metal homeostasis and protein aggregate for many diseases. Their dual roles as defenders in inflammation and neurodegeneration, and as suppressors and facilitators in cancer, highlight the complex nature of their biological role.