Structure and function of vertebrate metallothioneins

In 1957, Margoshes and Vallee reported on the isolation of a protein from horse kidney, which showed a high affinity for cadmium, and soon thereafter the protein was named metallothionein (MT) by the leading scientists Kägi and Vallee. Fifty years of intense research has dissected out many of the biochemical, molecular, and genetic aspects of these proteins, yet not that much is understood on its physiological putative functions. Being a highly conserved family of proteins would suggest essential biological functions, but these may be dispensable and/or assumed by other proteins as demonstrated by the phenotype of knock-out mice in normal conditions. Nevertheless, under challenging conditions (such as tissue injury) a strong phenotype appears that is suggestive of important physiological functions. This has been particularly well shown in the brain, where antiinflammatory, antioxidant and antiapoptotic effects of MT have been demonstrated. To date, the results gathered strongly support a therapeutic value of these proteins that deserve attention in clinical studies.