Endogenous mechanisms of neuroprotection: role of zinc, copper, and carnosine.

Zinc and copper are endogenous transition metals that can be synaptically released during neuronal activity. Synaptically released zinc and copper probably function to modulate neuronal excitability under normal conditions. However, zinc and copper also can be neurotoxic, and it has been proposed that they may contribute to the neuropathology associated with a variety of conditions, such as Alzheimer's disease, stroke, and seizures. Recently, we demonstrated that carnosine, a dipeptide expressed in glial cells throughout the brain as well as in neuronal pathways of the visual and olfactory systems, can modulate the effects of zinc and copper on neuronal excitability. This result led us to hypothesize that carnosine may modulate the neurotoxic effects of zinc and copper as well. Our results demonstrate that carnosine can rescue neurons from zinc- and copper-mediated neurotoxicity and suggest that one function of carnosine may be as an endogenous neuroprotective agent.