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.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“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
Cites
Free radicals in biology and medicine
Gutteridge, J. M. C. (1991) · General Pharmacology The Vascular System · doi:10.1016/0306-3623(91)90478-o · Cited by 17,178
NITRIC OXIDE AND MACROPHAGE FUNCTION
MacMicking, J. D., Xie, Q. W., & Nathan, C. (1997) · Annual Review of Immunology · doi:10.1146/annurev.immunol.15.1.323 · Cited by 4,245
Reactive astrocytes: cellular and molecular cues to biological function
Ridet, J., Privat, A., Malhotra, S. K., & Gage, F. H. (1997) · Trends in Neurosciences · doi:10.1016/s0166-2236(97)01139-9 · Cited by 1,766
Regulation of biosynthesis of nitric oxide.
Nathan, C., & Xie, Q. W. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)36703-0 · Cited by 1,669
MacMicking, J. D., Nathan, C., Hom, G. J., Chartrain, N. A., Fletcher, D. S., Trumbauer, M. E., Stevens, K. A., Xie, Q. W., Sokol, K. A., Hutchinson, N. I., et al. (1995) · Cell · doi:10.1016/0092-8674(95)90085-3 · Cited by 1,445
Bredt, D. S., Glatt, C. E., Hwang, P. M., Fotuhi, M., Dawson, T. M., & Snyder, S. H. (1991) · Neuron · doi:10.1016/0896-6273(91)90374-9 · Cited by 1,359
Self-citationTargeted disruption of the neuronal nitric oxide synthase gene
Huang, P. L., Dawson, T. M., Bredt, D. S., Snyder, S. H., & Fishman, M. C. (1993) · Cell · doi:10.1016/0092-8674(93)90615-w · Cited by 1,303
Self-citationGases as biological messengers: nitric oxide and carbon monoxide in the brain
Dawson, T., & Snyder, S. (1994) · The Journal of Neuroscience · doi:10.1523/jneurosci.14-09-05147.1994 · Cited by 1,043
Self-citationMICROGLIA AS MEDIATORS OF INFLAMMATORY AND DEGENERATIVE DISEASES
González-Scarano, F., & Baltuch, G. (1999) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.22.1.219 · Cited by 984
New stereological methods for counting neurons
West, M. J. (1993) · Neurobiology of Aging · doi:10.1016/0197-4580(93)90112-o · Cited by 940
Kinetics of superoxide dismutase- and iron-catalyzed nitration of phenolics by peroxynitrite
Beckman, J. S., Ischiropoulos, H., Zhu, L., van der Woerd, M., Smith, C. D. L., Chen, J., Harrison, J. G., Martin, J. C., & Tsai, M. (1992) · Archives of Biochemistry and Biophysics · doi:10.1016/0003-9861(92)90432-v · Cited by 768
Superoxide and peroxynitrite generation from inducible nitric oxide synthase in macrophages
Xia, Y., & Zweier, J. L. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.13.6954 · Cited by 691
DINERMAN, J. L., Dawson, T. M., Schell, M. J., Snowman, A. M., & Snyder, S. H. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.10.4214 · Cited by 648
Self-citationSynthesis of nitric oxide in CNS glial cells
Murphy, S. P., Simmons, M. L., Agulló, L., Garcı́a, A., Feinstein, D. L., Galea, E., Reis, D. J., Minc‐Golomb, D., & Schwartz, J. P. (1993) · Trends in Neurosciences · doi:10.1016/0166-2236(93)90109-y · Cited by 633
Przedborski, S., Jackson-Lewis, V. R., Yokoyama, R., Shibata, T., Dawson, V. L., & Dawson, T. M. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.10.4565 · Cited by 624
Self-citationJackson-Lewis, V. R., Jakowec, M. W., Burke, R. E., & Przedborski, S. (1995) · Neurodegeneration · doi:10.1016/1055-8330(95)90015-2 · Cited by 609
Self-citationCloned and expressed macrophage nitric oxide synthase contrasts with the brain enzyme.
Lowenstein, C. J., Glatt, C. S., Bredt, D. S., & Snyder, S. H. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.15.6711 · Cited by 600
Nitric oxide synthase and neuronal vulnerability in parkinson's disease
Hunot, S., Boissière, F., Faucheux, B., Brugg, B., Mouatt-Prigent, A., Agid, Y., & Hirsch, E. C. (1996) · Neuroscience · doi:10.1016/0306-4522(95)00578-1 · Cited by 595
Induction of Nitric Oxide Synthase in Glial Cells
Simmons, M. L., & Murphy, S. P. (1992) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1992.tb08328.x · Cited by 490
Nathan, C., & Root, R. K. (1977) · The Journal of Experimental Medicine · doi:10.1084/jem.146.6.1648 · Cited by 485
Induction of calcium-independent nitric oxide synthase activity in primary rat glial cultures.
Galea, E., Feinstein, D. L., & Reis, D. J. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.22.10945 · Cited by 478
Hunot, S., Dugas, N., Faucheux, B. A., Hartmann, A., Tardieu, M., Debré, P., Agid, Y., Dugas, B., & Hirsch, É. C. (1999) · Journal of Neuroscience · doi:10.1523/jneurosci.19-09-03440.1999 · Cited by 473
Inhibition of neuronal nitric oxide synthase prevents MPTP–induced parkinsonism in baboons
Hantraye, P., Brouillet, E., Ferrante, R. J., Palfi, S., Dolan, R., Matthews, R. T., & Beal, M. F. (1996) · Nature Medicine · doi:10.1038/nm0996-1017 · Cited by 422
Immunologic NO Synthase: Elevation in Severe AIDS Dementia and Induction by HIV-1 gp41
Adamson, D. C., Wildemann, B., Sasaki, M., Glass, J. D., McArthur, J. C., Christov, V. I., Dawson, T. M., & Dawson, V. L. (1996) · Science · doi:10.1126/science.274.5294.1917 · Cited by 418
Self-citationSchulz, J. B., Matthews, R. T., Muqit, M. M. K., Browne, S. E., & Beal, M. F. (1995) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1995.64020936.x · Cited by 417
Ara, J. E., Przedborski, S., Naini, A., Jackson-Lewis, V. R., Trifiletti, R. R., Horwitz, J., & Ischiropoulos, H. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.13.7659 · Cited by 414
Self-citationPakkenberg, B., Møller, A., Gundersen, H. J. G., Dam, A. M., & Pakkenberg, H. (1991) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.54.1.30 · Cited by 408
Mandir, A. S., Przedborski, S., Jackson-Lewis, V., Wang, Z.-Q., Simbulan-Rosenthal, C. M., Smulson, M. E., Hoffman, B. E., Guastella, D. B., Dawson, V. L., & Dawson, T. M. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.10.5774 · Cited by 382
Self-citationAnimal Models of Action Tremor
Elble, R. J. (2008) · Movement Disorders · doi:10.1002/mds.870131306 · Cited by 381
Glial cells and inflammation in parkinson's disease: A role in neurodegeneration?
Hirsch, É. C., Hunot, S., Damier, P., & Faucheux, B. A. (1998) · Annals of Neurology · doi:10.1002/ana.410440717 · Cited by 334
Kostić, V., Przedborski, S., Flaster, E. R., & Šternić, N. (1991) · Neurology · doi:10.1212/wnl.41.2_part_1.202 · Cited by 298
Self-citationMPTP: current concepts and controversies.
Langston, J. W., & Irwin, I. (1986) · PubMed · Cited by 234
Almer, G., Vukosavić, S., Romero, N. B., & Przedborski, S. (1999) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1999.0722415.x · Cited by 231
Self-citationChapter 36: Astrocytes and Parkinson's disease
Forno, L. S., DeLanney, L. E., Irwin, I., Monte, D. A. D., & Langston, J. W. (1992) · Progress in brain research · doi:10.1016/s0079-6123(08)61770-7 · Cited by 230
Marked Induction of Calcium-Independent Nitric Oxide Synthase Activity after Focal Cerebral Ischemia
Iadecola, C., Xu, X., Zhang, F., El‐Fakahany, E. E., & Ross, M. E. (1995) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.1995.6 · Cited by 216
Langston, J. W., & Irwin, I. (1986) · Clinical Neuropharmacology · doi:10.1097/00002826-198612000-00001 · Cited by 199
[19] Antibodies that recognize nitrotyrosine
Ye, Y. Z., Strong, M. J., Huang, Z., & Beckman, J. S. (1996) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(96)69022-3 · Cited by 189
NITRIC OXIDE SYNTHASE: Role as a Transmitter/Mediator in the Brain and Endocrine System
Dawson, T. M., & Dawson, V. L. (1996) · Annual Review of Medicine · doi:10.1146/annurev.med.47.1.219 · Cited by 167
Self-citationFree radicals in biology and medicine, second edition
Halliwell, B. B., & Gutteridge, J. M. C. (1991) · Free Radical Biology and Medicine · doi:10.1016/0891-5849(91)90055-8 · Cited by 160
Giovanni, A., Sieber, B.-A., Heikkila, R. E., & Sonsalla, P. K. (1991) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)24767-x · Cited by 115
Schumann, R. R., Pfeil, D., Freyer, D., Bürger, W., Lamping, N., Kirschning, C. J., Göbel, U. B., & Weber, J. R. (1998) · Glia · doi:10.1002/(sici)1098-1136(199803)22:3 · Cited by 92
Keilhoff, G., Seidel, B., Noack, H., Tischmeyer, W., Staněk, D., & Wolf, G. L. (1996) · Neuroscience · doi:10.1016/0306-4522(96)00330-2 · Cited by 88
Activated astrocytes of the mouse hippocampus contain high levels of NADPH-diaphorase
Wallace, M. N., & Fredens, K. (1992) · Neuroreport · doi:10.1097/00001756-199211000-00001 · Cited by 81
Matthews, R. T., Yang, L., & Beal, M. F. (1997) · Experimental Neurology · doi:10.1006/exnr.1996.6406 · Cited by 79
Fogel, R., Zhang, X., & Renehan, W. E. (1996) · The Journal of Comparative Neurology · doi:10.1002/(sici)1096-9861(19960101)364:1 · Cited by 65
Leonard, C. S., Kerman, I. A., Blaha, G., Taveras, E. M., & Taylor, B. J. (1995) · The Journal of Comparative Neurology · doi:10.1002/cne.903620309 · Cited by 64
Hara, H., Waeber, C., Huang, P. L., Fujii, M., Fishman, M. C., & Moskowitz, M. A. (1996) · Neuroscience · doi:10.1016/0306-4522(96)00313-2 · Cited by 63
Experimental developments in movement disorders: update on proposed free radical mechanisms
Przedborski, S., & Jackson-Lewis, V. R. (1998) · Current Opinion in Neurology · doi:10.1097/00019052-199808000-00009 · Cited by 45
Self-citationAsmus, S. E., & Newman, S. W. (1994) · Journal of Neurobiology · doi:10.1002/neu.480250207 · Cited by 28
Dugas, N., Palacios‐Callender, M., Dugas, B., Riveros‐Moreno, V., Delfraissy, J. F., Kolb, J. P., & Moncada, S. (1998) · Cytokine · doi:10.1006/cyto.1998.0352 · Cited by 24
Generation of isoform-specific antibodies to nitric oxide synthases
Dawson, T. M., & Dawson, V. L. (1996) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(96)68037-9 · Cited by 5
Self-citation
Research works printed but not linked: 2
- Fahn, S. in Cecil's Textbook of Medicine vol.18 (eds. Wyngaarden, J.B. & Smith, L.H.Jr.) 2143–2147 (Saunders, Philadelphia, 1988).
- Przedborski, S. & Jackson-Lewis, V. Mechanisms of MPTP toxicity. Mov. Disord. 13, 35– 38 (1998).
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
