Metallothionein expression and roles in the central nervous system

Metallothioneins (MTs) are low-molecular-weight (6-7kD) nonenzymatic proteins (60-68 amino acid residues, 25-30% being cysteine) ubiquitously expressed in the animal kingdom. In the central nervous system (CNS), three MT isoforms are known, namely MT-I, MT-II, andMT-III. MT-I andMT-II (MT-I+II) are regulated and expressed coordinately and are currently the best characterized MT isoforms. This review will focus on the expression and roles of MT-I+II in the CNS. MT-I+II are implicated in diverse physiological and pathophysiological functions, such as metal ion metabolism, regulation of the CNS inflammatory response, protection against reactive oxygen species and oxidative stress, reduction of apoptotic cell death, and stimulation of neuroregeneration and brain tissue repair in vivo. Accordingly, brain tissue damage and neuro degeneration during pathological conditions and the accompanying mortality and clinical symptoms are altogether significantly increased in MT-I+II deficient mice, while the opposite is observed after medical MT-II treatment and in MT-I overexpressing mice. Consequently, MT-I+II are likely essential factors in CNS disorders, which suggests a potential therapeutic use of these proteins.Biomedical Reviews 2002; 13: 1-15