Metallothionein's role in oxidative stress: A pathway to innovative treatments

Metallothioneins (MTs), a family of cysteine-rich, low-molecular-weight proteins with high metal-binding affinity, are promising candidates for preventing and treating oxidative stress-related diseases. MTs confer protection against diverse pathologies, including diabetes and its complications, aging-related disorders, and cancer. Their mechanisms of action encompass scavenging reactive oxygen and nitrogen species (ROS/RNS), regulating metal ion homeostasis, and suppressing inflammatory responses and apoptosis. The expression of MTs is tightly regulated by multiple cis-acting elements, such as metal, antioxidant, and glucocorticoid response elements, as well as by epigenetic mechanisms. Furthermore, MTs modulate critical signaling pathways-including MAPK, NF-κB, and JAK/STAT-thereby participating in cellular stress adaptation. Recent advances have introduced novel strategies for inducing MT expression, including nanomaterial-based delivery systems and molecular chaperones, thereby enabling targeted therapeutic applications. This review aims to synthesize available evidence, elucidate the central role of MT in oxidative stress-related diseases, and highlight its translational potential as a therapeutic target.