Localization, regulation, and function of metallothionein-III/growth inhibitory factor in the brain

The metallothionein (MT) family is a class of low molecular, intracellular, and cysteine-rich proteins with a high affinity for metals. Although the f irst of these proteins was discovered nearly 40 years ago, their functional significance remains obscure, Four major isoforms (MT-I, MT-II, MT-III, an d MT-IV) have been identified in mammals. MT-I and MT-II are ubiquitously e xpressed in various organs including the brain, while expression of MT-III and MT-IV is restricted in specific organs. MT-III was detected predominant ly in the brain, and characterized as a central nervous system-specific iso mer, The role of MTs in the central nervous system has become an intense fo cus of scientific research. An isomer of MTs, MT-III, of particular interes t, was originally discovered as a growth inhibitory factor, and has been fo und to be markedly reduced in the brain of patients with Alzheimer's diseas e and several other neurodegenerative diseases, MT-III fulfills unique biol ogical roles in homeostasis of the central nervous system and in the etiolo gy of neuropathological disorders.