Manganese Superoxide Dismutase Overexpression Attenuates MPTP Toxicity
Open accessAbstract
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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The neurotoxicity of MPTP was significantly reduced in SOD2-overexpressing mice compared to wild-type mice.
“the neurotoxicity of MPTP was significantly reduced in SOD2-overexpressing mice compared to wild-type mice [81]”
From Healthy Human Fecal Microbiota Transplantation into Mice Attenuates MPTP-Induced Neurotoxicity <i>via</i> AMPK/SOD2 Pathway (2023) · cites this paper as [81]
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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
- green
- doaj.org
- Licence
- 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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