The DOI matches its Crossref record; 51 of the 53 references it cites were found in a registry or an index.
Inducible nitric oxide synthase stimulates dopaminergic neurodegeneration in the MPTP model of Parkinson disease
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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“In recent years, several studies have linked nitric oxide as a key mediator in numerous neurodegenerative diseases, such as Parkinson’s disease (PD), Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), Huntington’s disease (HD) and ischemic brain injury (stroke).”
From The Role of Reactive Species on Innate Immunity (2022) · cites this paper as [143]
In the citing paper
“This dual action makes it a contributing player in pathophysiology, but also makes the development of effective treatments for neurodegenerative diseases particularly difficult [141,142,143,144,145].”
From The Role of Reactive Species on Innate Immunity (2022) · cites this paper as [143]
Citations
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Self-citationTargeted disruption of the neuronal nitric oxide synthase gene
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- Fahn, S. in Cecil's Textbook of Medicine vol.18 (eds. Wyngaarden, J.B. & Smith, L.H.Jr.) 2143–2147 (Saunders, Philadelphia, 1988).
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Cited by
Sorted by citations
Roles of CHOP/GADD153 in endoplasmic reticulum stress
Oyadomari, S., & Mori, M. (2003) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4401373 · Cited by 2,879
“stress, and overexpression of parkin confers resistance to both ER stress and mutant a-synuclein-induced toxicity.(104,105)”
BackgroundDifferential Roles of M1 and M2 Microglia in Neurodegenerative Diseases
Tang, Y., & Le, W. (2016) · Molecular Neurobiology · doi:10.1007/s12035-014-9070-5 · Cited by 2,190
“Similarly, typical characteristics of M1 phenotype including the activation of NADPH oxidase and NF-κB pathways, as well as the release of various pro-inflammatory mediators were observed in the MPTP-intoxicated models [79–81].”
BackgroundOxidative stress in Parkinson's disease
Jenner, P. (2003) · Annals of Neurology · doi:10.1002/ana.10483 · Cited by 2,053
Neuroinflammation in Parkinson’s disease: A target for neuroprotection?
Hirsch, E. C., & Hunot, S. (2009) · The Lancet Neurology · doi:10.1016/s1474-4422(09)70062-6 · Cited by 1,984
Oxidative stress in neurodegeneration: Cause or consequence?
Andersen, J. K. (2004) · Nature Medicine · doi:10.1038/nrn1434 · Cited by 1,869
Metadata
- 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
- Venue
- Nature Medicine
- Published
- 1999-12
- Volume
- 5
- Issue
- 12
- Pages
- 1403-1409
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- 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
- 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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