Cited by 142Parkinson's Disease Mechanisms and TreatmentsGlutathione Transferases and PolymorphismsMitochondrial Function and Pathology

Manganese Superoxide Dismutase Overexpression Attenuates MPTP Toxicity

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Klivenyi, Peter, St. Clair, Daret, Wermer, Marike, Yen, Hsin-Chuan, Oberley, Terry, Yang, Lichuan, Beal, M.Flint·1998·Neurobiology of Disease

Abstract

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.

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Crossref · 10.1006/nbdi.1998.0191

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Authors
Klivenyi, P., St. Clair, D., Wermer, M., Yen, H.-C., Oberley, T., Yang, L., & Beal, M. F.
Affiliations
  • Harvard University (US)
  • University of Kentucky (US)
  • University of Wisconsin–Madison (US)
Venue
Neurobiology of Disease
Publisher
Elsevier BV
Published
1998-10
Volume
5
Issue
4
Pages
253-258
ISSN
0969-9961 (ISSN-L)
OpenAlex
W2009842580
Cited by
142
References
25
Citations by year
2024: 3 · 2023: 2 · 2022: 3 · 2021: 1 · 2020: 3 · 2019: 1 · 2018: 2 · 2017: 5 · 2016: 5 · 2015: 3 · 2014: 6 · 2013: 3 · 2012: 6
FWCI
5.93
Type
journal article
Language
en
Open access
Locations
  • Neurobiology of Disease (publishedVersion)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Institutes of Health (5r01ns032365-03, 5p01ns031579-05)
  • National Cancer Institute (CA49797)
  • National Institute of Neurological Disorders and Stroke (NS31579, NS32365)
Topics
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glutathione Transferases and Polymorphisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
Keywords
manganese superoxide dismutase, MPTP-induced neurotoxicity, Parkinson's disease, mitochondrial dysfunction, oxidative stress, superoxide, dopamine levels, MPP+, nitrotyrosine, neuroprotection, transgenic mice, antioxidant enzymes
MeSH terms
Animals, Brain, Brain Diseases, Cerebral Cortex, Dopamine, Humans, Mice, Transgenic, Mitochondria, Neurons, Superoxide Dismutase, 3,4-Dihydroxyphenylacetic Acid, Dopamine Agents, 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine, 1-Methyl-4-phenylpyridinium, Gene Expression, Microscopy, Immunoelectron, Transgenes, Mice

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