Cited by 1,046Parkinson's Disease Mechanisms and TreatmentsNuclear Receptors and SignalingNeuroinflammation and Neurodegeneration Mechanisms

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Inducible nitric oxide synthase stimulates dopaminergic neurodegeneration in the MPTP model of Parkinson disease

Liberatore, Gabriel T., Jackson-Lewis, Vernice, Vukosavic, Slobodanka, Mandir, Allen S., Vila, Miquel, McAuliffe, W. Geoffrey, Dawson, Valina L., Dawson, Ted M., Przedborski, Serge·1999·Nature Medicine

DOI 10.1038/70978

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Abstract

MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) damages dopaminergic neurons as seen in Parkinson disease. Here we show that after administration of MPTP to mice, there was a robust gliosis in the substantia nigra pars compacta associated with significant upregulation of inducible nitric oxide synthase (iNOS). These changes preceded or paralleled MPTP-induced dopaminergic neurodegeneration. We also show that mutant mice lacking the iNOS gene were significantly more resistant to MPTP than their wild-type littermates. This study demonstrates that iNOS is important in the MPTP neurotoxic process and indicates that inhibitors of iNOS may provide protective benefit in the treatment of Parkinson disease.

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Authors: Liberatore, G. T., Jackson-Lewis, V., Vukosavic, S., Mandir, A. S., Vila, M., McAuliffe, W. G., Dawson, V. L., Dawson, T. M., & Przedborski, S.
Affiliations: Columbia University (US)
Johns Hopkins University (US)
Rutgers, The State University of New Jersey (US)
Corresponding author: Przedborski, Serge
ORCID: Vila, Miquel
Dawson, Valina L.
Dawson, Ted M.
Przedborski, Serge
Venue: Nature Medicine
Publisher: Springer Science and Business Media LLC
Published: 1999-12
Volume: 5
Issue: 12
Pages: 1403-1409
ISSN: 1078-8956 (ISSN-L)
1546-170X
DOI: 10.1038/70978
OpenAlex: W1530199299
Cited by: 1,046
References: 53
Citations by year: 2026: 9 · 2025: 11 · 2024: 10 · 2023: 19 · 2022: 20 · 2021: 27 · 2020: 22 · 2019: 31 · 2018: 43 · 2017: 35 · 2016: 44 · 2015: 41 · 2014: 45 · 2013: 49 · 2012: 52
FWCI: 25.39
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (unspecified)
Locations: Nature Medicine (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (5r29ns037345-05)
National Institute of Neurological Disorders and Stroke (P50-NS38370, R01 NS 38586, R29 NS37345, R01NS038586, P50NS038370)
Topics: Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Receptors and Signaling
Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords: inducible nitric oxide synthase, MPTP, Parkinson's disease, dopaminergic neuron loss, substantia nigra pars compacta, gliosis, iNOS knockout mice, neuroprotection, iNOS inhibitors, neurotoxicity
MeSH terms: Animals, Disease Models, Animal, Dopamine, Enzyme Inhibitors, Male, Mice, Inbred C57BL, Nerve Degeneration, Parkinson Disease, RNA, Messenger, Gene Expression, Microglia, Mice, Knockout, Nitric Oxide Synthase, MPTP Poisoning, Mice, Nitric Oxide Synthase Type II

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Inducible nitric oxide synthase stimulates dopaminergic neurodegeneration in the MPTP model of Parkinson disease

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