Unlocking the brain's zinc code: implications for cognitive function and disease.

Zn transport across neuronal membranes relies on two classes of transition metal transporters: the ZnT (SLC30) and ZIP (SLC39) families. These proteins function to decrease and increase cytosolic Zn levels, respectively. Dysfunction of ZnT and ZIP transporters can alter intracellular Zn levels resulting in deleterious effects. In neurons, imbalances in Zn levels have been implicated as risk factors in conditions such as Alzheimer's disease and neurodegeneration, highlighting the pivotal role of Zn homeostasis in neuropathologies. In addition, Zn modulates the function of plasma membrane proteins, including ion channels and receptors. Changes in Zn levels, on both sides of the plasma membrane, profoundly impact signaling pathways governing cell development, differentiation, and survival. This review is focused on recent developments of neuronal Zn homeostasis, including the impact of Zn dyshomeostasis in neurological disorders, therapeutic approaches, and the increasingly recognized role of Zn as a neurotransmitter in the brain.