Zn2+: a novel ionic mediator of neural injury in brain disease

Zn2+ is the second most prevalent trace element in the body and is present in particularly large concentrations in the mammalian brain. Although Zn2is a cofactor for many enzymes in all tissues, a unique feature of brain Zn 2+ is its vesicular localization in presynaptic terminals, where its releas e is dependent on neural activity. Although the physiological significance of synaptic Zn2+ release is little understood, it probably plays a modulato ry role in synaptic transmission. Furthermore, several lines of evidence su pport the idea that, upon excessive synaptic Zn2+ release, its accumulation in postsynaptic neurons contributes to the selective neuronal loss that is associated with certain acute conditions, including epilepsy and transient global ischaemia. More speculatively, Zn2+ dis-homeostasis might also cont ribute to some degenerative conditions, including Alzheimer's disease. Furt her elucidation of the pathological actions of Zn2+ in the brain should res ult in new therapeutic approaches to these conditions.