Role and regulation of copper and zinc transport proteins in the central nervous system

Abstract

The trace elements copper and zinc are essential for the molecular and physiological functions of the central nervous system (CNS). These cations act as cofactors for enzymes that regulate every aspect of CNS function, including neuronal development and plasticity, neurotransmitter synthesis and processing, cellular metabolism and energy production, and gene expression. Imbalances in zinc have been associated with a variety of clinical disorders, including Alzheimer's disease (AD) and Parkinson's disease. Zinc has also been implicated in the neuronal damage and death associated with ischemia, seizure disorders, and brain trauma. Genetic disorders characterized by copper toxicity and copper deficiency have severe neurological consequences. Thus, it is important that subcellular copper and zinc balance be maintained precisely. This task is accomplished by several families of metal-specific transport proteins. For each metal, this chapter will begin with a brief introduction to the role of this metal in the CNS. This will be followed by the function and regulation of the known transport proteins involved in cellular uptake, intracellular trafficking, and cellular export in the CNS. There will also be discussions of the clinical implications of zinc and copper transporter abnormalities as well as the possible ways that an understanding of these transporters could lead to the development of new treatments for a variety of neurological disorders. © 2007 Springer-Verlag US.