Zn(2+): a novel ionic mediator of neural injury in brain disease

Trends Pharmacol Sci. 2000 Oct;21(10):395-401. doi: 10.1016/s0165-6147(00)01541-8.


Zn(2+) is the second most prevalent trace element in the body and is present in particularly large concentrations in the mammalian brain. Although Zn(2+) is a cofactor for many enzymes in all tissues, a unique feature of brain Zn(2+) is its vesicular localization in presynaptic terminals, where its release is dependent on neural activity. Although the physiological significance of synaptic Zn(2+) release is little understood, it probably plays a modulatory role in synaptic transmission. Furthermore, several lines of evidence support the idea that, upon excessive synaptic Zn(2+) 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, Zn(2+) dis-homeostasis might also contribute to some degenerative conditions, including Alzheimer's disease. Further elucidation of the pathological actions of Zn(2+) in the brain should result in new therapeutic approaches to these conditions.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Brain Diseases / metabolism*
  • Calcium Channels / metabolism
  • Humans
  • Neurodegenerative Diseases / etiology
  • Neurodegenerative Diseases / metabolism
  • Neurons / metabolism*
  • Presynaptic Terminals / metabolism*
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Signal Transduction / physiology
  • Zinc / metabolism
  • Zinc / physiology*


  • Calcium Channels
  • Receptors, N-Methyl-D-Aspartate
  • Zinc