Manganese superoxide dismutase overexpression attenuates MPTP toxicity

Peter Klivenyi, Daret St. Clair, Marike Wermer, Hsin Chuan Yen, Terry Oberley, Lichuan Yang, M. Flint Beal

Research output: Contribution to journalArticlepeer-review

133 Scopus citations


There is substantial evidence implicating mitochondrial dysfunction and free radical generation in the neurotoxicity of MPTP. Manganese superoxide dismutase (MnSOD) is the primary antioxidant enzyme protecting against superoxide radicals produced within mitochondria. Overexpression of human MnSOD in transgenic mice resulted in increased MnSOD localized to mitochondria in neurons and a 50% increase in total MnSOD activity in brain homogenates. We found that MPTP toxicity was significantly attenuated in the MnSOD transgenic mice which overexpress the human manganese superoxide dismutase gene, with these mice showing threefold greater dopamine levels than controls following MPTP. There were no alterations in MPP+ levels, suggesting that the effects were not due to altered metabolism of MPTP. A significant increase in 3-nitrotyrosine levels was seen in littermate controls but not in transgenic mice overexpressing human MnSOD. These results provide further evidence implicating mitochondrial dysfunction and oxidative damage in the pathogenesis of MPTP neurotoxicity.

Original languageEnglish
Pages (from-to)253-258
Number of pages6
JournalNeurobiology of Disease
Issue number4
StatePublished - Oct 1998

Bibliographical note

Funding Information:
The secretarial assistance of Sharon Melanson is greatly acknowledged. This work was supported by NIH Grants NS32365 and NS 31579 (M.F.B.) and CA49797 and CA59835 (D.S.C.).


  • Free radicals
  • MPTP
  • Oxidative damage
  • Parkinson's disease
  • Superoxide dismutase

ASJC Scopus subject areas

  • Neurology


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