Molecular Medicine

, Volume 13, Issue 7–8, pp 350–355 | Cite as

Intracellular Zinc Release, 12-Lipoxygenase Activation and MAPK Dependent Neuronal and Oligodendroglial Death

  • Yumin Zhang
  • Elias Aizenman
  • Donald B. DeFranco
  • Paul A. Rosenberg


Zinc translocation from presynaptic nerve terminals to postsynaptic neurons has generally been considered the critical step leading to the accumulation of intracellular free zinc and subsequent neuronal injury. Recent evidence, however, strongly suggests that the liberation of zinc from intracellular stores upon oxidative and nitrative stimulation contributes significantly to the toxicity of this metal not only to neurons, but also to oligodendrocytes. The exact cell death signaling pathways triggered by zinc are beginning to be deciphered. In this review, we describe how the activation of 12-lipoxygenase and mitogen-activated protein kinase (MAPK) contribute to the toxicity of liberated zinc to neurons and oligodendrocytes.



This work is supported by grants from the United Cerebral Palsy Foundation (R-759 to Y.Z.), the National Multiple Sclerosis Society (RG3741 to Y.Z.) and the National Institutes of Health (NS043277 to E.A., NS038319 to D.B.D., and NS038475 to P.A.R.).


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Copyright information

© Feinstein Institute for Medical Research 2007

Authors and Affiliations

  • Yumin Zhang
    • 1
  • Elias Aizenman
    • 2
  • Donald B. DeFranco
    • 3
  • Paul A. Rosenberg
    • 4
  1. 1.Department of Anatomy Physiology and Genetics and Program in NeuroscienceUniformed Services University of the Health SciencesBethesdaUSA
  2. 2.Department of NeurobiologyUniversity of Pittsburgh School of MedicinePittsburghUSA
  3. 3.Department of Pharmacology and Pittsburgh Institute for Neurodegenerative DiseasesUniversity of Pittsburgh School of MedicinePittsburghUSA
  4. 4.Department of Neurology and Program in NeuroscienceChildren’s Hospital and Harvard Medical SchoolBostonUSA

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