Coenzyme Q10 and nicotinamide and a free radical spin trap protect against MPTP neurotoxicity
Abstract
1-Methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) produces Parkinsonism in both experimental animals and in man. MPTP is metabolized to 1-methyl-4-phenylpridinium, an inhibitor of mitochondrial complex I. MPTP administration produces ATP depletions in vivo, which may lead to secondary excitotoxicity and free radical generation. If this is the case then agents which improve mitochondrial function or free radical scavengers should attenuate MPTP neurotoxicity. In the present experiments three regimens of MPTP administration produced varying degrees of striatal dopamine depletion. A combination of coenzyme Q10 and nicotinamide protected against both mild and moderate depletion of dopamine. In the MPTP regimen which produced mild dopamine depletion nicotinamide or the free radical spin trap N-tert-butyl-alpha-(2-sulfophenyl)-nitrone were also effective. There was no protection with a MPTP regimen which produced severe dopamine depletion. These results show that agents which improve mitochondrial energy production (coenzyme Q10 and nicotinamide) and free radical scavengers can attenuate mild to moderate MPTP neurotoxicity.
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Nicotinamide prevents MPTP induced neurodegeneration in mice.
“Nicotinamide prevents MPTP induced neurodegeneration in mice139.”
From Mitochondrial Approaches for Neuroprotection (2008) · cites this paper as [139]
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- Authors
- Schulz, J. B., Ross Henshaw, D., Matthews, R. T., & Flint Beal, M.
- Affiliations
- Harvard University (US)
- Venue
- Experimental Neurology
- Publisher
- Elsevier BV
- Published
- 1995-04
- Volume
- 132
- Issue
- 2
- Pages
- 279-283
- ISSN
- 0014-4886 (ISSN-L)
- OpenAlex
- W2014192866
- Cited by
- 103
- References
- 30
- Citations by year
- 2025: 1 · 2022: 2 · 2020: 2 · 2019: 1 · 2017: 1 · 2015: 1 · 2014: 2 · 2013: 2 · 2012: 9
- FWCI
- 4.88
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Experimental Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5p01ns031579-05)
- National Institute of Neurological Disorders and Stroke (NS 16367, NS31579)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Coenzyme Q10 studies and effects
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
- Keywords
- MPTP-induced neurotoxicity, coenzyme Q10, nicotinamide, parkinsonism, striatal dopamine depletion, mitochondrial complex I inhibition, mitochondrial energy production, radical scavengers, excitotoxicity, ATP depletion
- MeSH terms
- Animals, Benzenesulfonates, Coenzymes, Corpus Striatum, Free Radicals, Male, Mice, Inbred Strains, Niacinamide, Spin Labels, Ubiquinone, Neuroprotective Agents, MPTP Poisoning, Mice
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