Zinc (Zn, Zn2+) is an essential nutrient that has multiple fundamental functions in the developing and adult nervous system.1-5 Zinc is a structural and regulatory catalyst ion for all major classes of enzymes6; it stabilizes zinc-finger proteins involved in transcriptional regulation and protein maturation7, functions as an intracellular signaling molecule,5 and is released from glutamatergic terminals modulating several receptors and ion channels2,8-10 (Figure). Through these multiple mechanisms, Zn has a critical role in neurogenesis, cell survival, redox signaling, synaptic plasticity, and immune modulation.4,11-15 Zinc homeostasis is tightly regulated by Zn transport proteins of the ZIP (SLC30) and ZnT (SLC39) families16-18 and by its buffering by metallothioneins (MTs).19-21 Both deficiency and excess of Zn have deleterious effects in the nervous system.1,14,22,23 While Zn deficiency impairs neurogenesis12 and immune function,24 excessive accumulation of cytosolic Zn2+ triggers oxidative stress, mitochondrial dysfunction, protein misfolding, and other processes leading to cell toxicity and neurodegeneration.5,22,23,25-28 This brief review will focus on key aspects of Zn homeostasis and functions and its potential toxic effects in the nervous system.
