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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Several studies have linked nitric oxide as a key mediator in numerous neurodegenerative diseases, such as Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis, Huntington's disease and ischemic brain injury.
“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]
•NO's dual action makes it a contributing player in pathophysiology and makes development of effective treatments for neurodegenerative diseases particularly difficult.
“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]
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ResultInflammatory neurodegeneration mediated by nitric oxide, glutamate, and mitochondria
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Translocator protein 18 kDa (TSPO): Molecular sensor of brain injury and repair
Chen, M.-K., & Guilarte, T. R. (2008) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2007.12.004 · Cited by 506 · see citing works
“On the other hand, astrocytes become activated sometime after microglia but they appear to have a more protracted period of activation than microglia (Chen et al., 2004; Guilarte 2004; Kuhlmann and Guilarte, 2000; Liberatore et al., 1999; McCann et al., 1996).”
BackgroundOxidative Stress in Parkinson's Disease
Zhou, C. H., Huang, Y., & Przedborski, S. (2008) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1427.023 · Cited by 453 · see citing works
Self-citationThe Role of Glial Reaction and Inflammation in Parkinson's Disease
Hirsch, É. C., Breidert, T., Rousselet, E., Hunot, S., Hartmann, A., & Michel, P. P. (2003) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2003.tb07478.x · Cited by 449 · see citing works
Glial cells as intrinsic components of non-cell-autonomous neurodegenerative disease
Lobsiger, C. S., & Cleveland, D. W. (2007) · Nature Neuroscience · doi:10.1038/nn1988 · Cited by 438 · see citing works
Induction of α-Synuclein Aggregation by Intracellular Nitrative Insult
Paxinou, E., Chen, Q., Weisse, M., Giasson, B. I., Norris, E. H., Rueter, S. M., Trojanowski, J. Q., Lee, V. M. ‐., & Ischiropoulos, H. (2001) · Journal of Neuroscience · doi:10.1523/jneurosci.21-20-08053.2001 · Cited by 440 · see citing works
“…in human neurodegenerative diseases as well as animal models of neurodegeneration has been provided (Smith et al., 1997; Ara et al., 1998; Good et al., 1998; Hensley et al., 1998; Liberatore et al., 1999; Duda et al., 2000b; Received June 7, 2001; revised July 31, 2001; accepted Aug. 8, 2001.”
BackgroundNeuroinflammation and Oxidation/Nitration of α-Synuclein Linked to Dopaminergic Neurodegeneration
Gao, H., Kotzbauer, P. T., Uryu, K., Leight, S., Trojanowski, J. Q., & Lee, V. M. ‐. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.0143-07.2008 · Cited by 435 · see citing works
“, 1999), and animal models of PD created by MPTP, 6-OHDA, or rotenone (Liberatore et al., 1999; Cicchetti et al., 2002; Sherer et al., 2003).”
BackgroundLinking Neuroinflammation and Neurodegeneration in Parkinson's Disease
Gelders, G., Baekelandt, V., & Van der Perren, A. (2018) · Journal of Immunology Research · doi:10.1155/2018/4784268 · Cited by 430 · see citing works
“This model also provided evidence for the direct involvement of activated microglia in the processes leading to neuronal cell death as microglial activation precedes neuronal degeneration [35, 61, 63].”
BackgroundHunot, S., Vila, M., Teismann, P., Davis, R. J., Hirsch, É. C., Przedborski, S., RAKIC, P. T., & Flavell, R. A. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0307453101 · Cited by 427 · see citing works
Self-citationGlia: Initiators and progressors of pathology in Parkinson's disease
Halliday, G. M., & Stevens, C. H. (2011) · Movement Disorders · doi:10.1002/mds.23455 · Cited by 423 · see citing works
“6-hydroxydopamine animal models and in MPTP mice lacking the iNOS gene.(88) Increased concentrations of the proinflammatory cytokines have been identified in the striatum, SN,(112) serum, and cerebrospinal fluid in patients with PD.”
BackgroundD-β-Hydroxybutyrate rescues mitochondrial respiration and mitigates features of Parkinson disease
Tieu, K., Perier, C., Caspersen, C., Teismann, P., Wu, D.-C., Yan, S.-D., Naini, A., Vila, M., Jackson-Lewis, V., Ramasamy, R., et al. (2003) · Journal of Clinical Investigation · doi:10.1172/jci200318797 · Cited by 497 · see citing works
Self-citationNeuroprotective activities of CD4+CD25+ regulatory T cells in an animal model of Parkinson’s disease
Reynolds, A. D., Banerjee, R., Liu, J., Gendelman, H. E., & Mosley, R. L. (2007) · Journal of Leukocyte Biology · doi:10.1189/jlb.0507296 · Cited by 422 · see citing works
“Of the microglial secretory factors known to influence secondary degeneration, TNF- and iNOS are implicated in stimulating the dopaminergic cell loss observed following MPTP intoxication [21].”
BackgroundReynolds, A. D., Stone, D. K., Hutter, J. A. L., Benner, E., Mosley, R., & Gendelman, H. E. (2010) · Journal of Immunology · doi:10.4049/jimmunol.0901852 · Cited by 391 · see citing works
“Total numbers of Mac-1 cells, CD4 T cells, and TH- and Nissl-stained neurons in the SN were estimated by stereological analysis with Stereo Investigator software (MBF Bioscience, Williston, VT), using the optical fractionator module (22).”
MethodOxidative Stress and Genetics in the Pathogenesis of Parkinson's Disease
Zhang, Y., Dawson, V. L., & Dawson, T. M. (2000) · Neurobiology of Disease · doi:10.1006/nbdi.2000.0319 · Cited by 406 · see citing works
Self-citationThe molecular bases of Alzheimer’s disease and other neurodegenerative disorders
Maccioni, R. B., Muñoz, J. P., & Barbeito, L. (2001) · Archives of Medical Research · doi:10.1016/s0188-4409(01)00316-2 · Cited by 474 · see citing works
Neuroinflammatory processes in Parkinson's disease
Hunot, S., & Hirsch, É. C. (2003) · Annals of Neurology · doi:10.1002/ana.10481 · Cited by 399 · see citing works
Nitric oxide and neuronal death
Brown, G. C. (2010) · Nitric Oxide · doi:10.1016/j.niox.2010.06.001 · Cited by 390 · see citing works
Plasma Urate and Risk of Parkinson's Disease
Weisskopf, M. G., O’Reilly, É. J., Chen, H., Schwarzschild, M. A., & Ascherio, A. (2007) · American Journal of Epidemiology · doi:10.1093/aje/kwm127 · Cited by 390 · see citing works
Neuroinflammation, oxidative stress, and the pathogenesis of Parkinson’s disease
Mosley, R. L., Benner, E. J., Kadiu, I., Thomas, M., Boska, M. D., Hasan, K. M., Laurie, C. D., & Gendelman, H. E. (2006) · Clinical Neuroscience Research · doi:10.1016/j.cnr.2006.09.006 · Cited by 388 · see citing works
“Ablation by genetic manipulation or inhibition with specific pharmaceutical agents protects nigral neurodegeneration induced by MPTP [96,228,229], LPS [222] or 6-OHDA [197], but is less active at protecting striatal termini [96,228].”
BackgroundInfluentialDehmer, T., Heneka, M. T., Sastre, M., DICHGANS, J., & Schulz, J. B. (2003) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2003.02210.x · Cited by 382 · see citing works
“Similar results were obtained by us and others in iNOS-deficient mice (Liberatore et al. 1999; Dehmer et al. 2000).”
BackgroundResultInfluentialThe MPTP model of Parkinson's disease
Smeyne, R. J., & Jackson-Lewis, V. R. (2004) · Molecular Brain Research · doi:10.1016/j.molbrainres.2004.09.017 · Cited by 377 · see citing works
Self-citationGao, H.-M., Zhang, F., Zhou, H., Kam, W., Wilson, B., & Hong, J.-S. (2011) · Environmental Health Perspectives · doi:10.1289/ehp.1003013 · Cited by 355 · see citing works
“Morphologic changes of microglia (the resident brain immune cells) and accumulation of pro inflammatory factors are associated with degenerating DA neurons in the substantia nigra (SN) of PD patients and various PD animal models (Liberatore et al. 1999; McGeer et al. 1988; Sherer et al. 2003).”
BackgroundBreidert, T., Callebert, J., Heneka, M. T., Landreth, G. E., Launay, J., & Hirsch, É. C. (2002) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2002.00990.x · Cited by 375 · see citing works
Vila, M., Jackson-Lewis, V. R., Vukosavić, S., Djaldetti, R., Liberatore, G. T., Offen, D., Korsmeyer, S. J., & Przedborski, S. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.051633998 · Cited by 372 · see citing works
Self-citationGao, H.-M., Zhou, H., Zhang, F., Wilson, B. C., Kam, W., & Hong, J.-S. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.3732-10.2011 · Cited by 369 · see citing works
“The expression of Mac1 is elevated in PD brains (Liberatore et al., 1999).”
BackgroundReactive Astrocytes As Therapeutic Targets for CNS Disorders
Hamby, M. E., & Sofroniew, M. V. (2010) · Neurotherapeutics · doi:10.1016/j.nurt.2010.07.003 · Cited by 367 · see citing works
Cellular pathology of Parkinson?s disease: astrocytes, microglia and inflammation
Teismann, P., & Schulz, J. B. (2004) · Cell and Tissue Research · doi:10.1007/s00441-004-0944-0 · Cited by 363 · see citing works
“…astrocytic activation parallels the time course of dopaminergic cell death in the SNpc as well as striatum and GFAP-expression remains upregulated even after most of dopaminergic neurons have died due to MPTP intoxication (Czlonkowska et al. 1996; Kohutnicka et al. 1998; Liberatore et al. 1999).”
BackgroundInfluentialNitrated α–Synuclein Immunity Accelerates Degeneration of Nigral Dopaminergic Neurons
Benner, E. J., Banerjee, R., Reynolds, A. D., Sherman, S., Писарев, В. М., Tsiperson, V., Nemachek, C., Ciborowski, P. S., Przedborski, S., Mosley, R. L., et al. (2008) · PLoS ONE · doi:10.1371/journal.pone.0001376 · Cited by 359 · see citing works
“nal loss in animal models of PD [66,67].”
BackgroundSelf-citationMonte, D. A. D. (2003) · The Lancet Neurology · doi:10.1016/s1474-4422(03)00501-5 · Cited by 356 · see citing works
Aberrant Protein S-Nitrosylation in Neurodegenerative Diseases
Nakamura, T., Tu, S., Akhtar, M. W., Sunico, C. R., Okamoto, S., & Lipton, S. A. (2013) · Neuron · doi:10.1016/j.neuron.2013.05.005 · Cited by 355 · see citing works
Regulation of Inducible Nitric Oxide Synthase Gene in Glial Cells
Saha, R. N., & Pahan, K. (2006) · Antioxidants and Redox Signaling · doi:10.1089/ars.2006.8.929 · Cited by 353 · see citing works
“Similarly, administration of MPTP in C57/BL6 mice leads to robust gliosis marked by upregulation of glial iNOS (83).”
Mechanism-Based Molecular Design of Highly Selective Fluorescence Probes for Nitrative Stress
Ueno, T., Urano, Y., Kojima, H., & Nagano, T. (2006) · Journal of the American Chemical Society · doi:10.1021/ja061972v · Cited by 351 · see citing works
MAPK signaling in neurodegeneration: influences of flavonoids and of nitric oxide
Schroeter, H., BOYD, C., SPENCER, J., WILLIAMS, R., Cadenas, E., & Rice-Evans, C. A. (2002) · Neurobiology of Aging · doi:10.1016/s0197-4580(02)00075-1 · Cited by 338 · see citing works
“Furthermore, microglia activation during neuroinflammation is associated with induction of inducible nitric oxide synthase (iNOS) expression leading to a large and sustained NO • production, which also appears to be causally linked to neuronal apoptosis and neurodegeneration [100,121].”
BackgroundDamage to dopaminergic neurons by oxidative stress in Parkinson's disease (Review)
Guo, J., Zhao, X., Li, Y., Li, G., & Liu, X. (2018) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2018.3406 · Cited by 347 · see citing works
“Microglia activation promotes the production of proinflammatory cytokines, which cause dopaminergic nigrostriatal neuron degeneration in MPTP models of PD (123).”
BackgroundPathogenesis of Parkinson's disease
Hirsch, E. C., Jenner, P., & Przedborski, S. (2013) · Movement Disorders · doi:10.1002/mds.25032 · Cited by 336 · see citing works
Self-citationWilms, H., Rosenstiel, P. C., Sievers, J., Deuschl, G., Zecca, L., & Lucius, R. (2003) · The FASEB Journal · doi:10.1096/fj.02-0314fje · Cited by 337 · see citing works
“Because levels of TNF-α are increased in postmortem brain and CSF from patients with PD, and TNF-α mediates cell death in a sensitive population of dopaminergic neurons in vitro (41), such results support the hypothesis of an involvement of proinflammatory cytokines in the degeneration of dopaminergic neurons in PD.”
BackgroundResultDeficiency of Inducible Nitric Oxide Synthase Protects Against MPTP Toxicity In Vivo
Dehmer, T., Lindenau, J. H., Haid, S., DICHGANS, J., & Schulz, J. B. (2000) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2000.0742213.x · Cited by 337 · see citing works
Bureau, G., Longpré, F., & Martinoli, M. (2007) · Journal of Neuroscience Research · doi:10.1002/jnr.21503 · Cited by 336 · see citing works
“Activation of microglia leads to an increase in the production of cytokines that could mediate neuronal apoptosis and precedes degeneration of DA nigrostriatal neurons in a PD mouse model (Liberatore et al., 1999).”
BackgroundPetroske, E., Meredith, G. E., Callen, S. E., Totterdell, S., & Lau, Y.-S. (2001) · Neuroscience · doi:10.1016/s0306-4522(01)00295-0 · Cited by 331 · see citing works
“, 1998), but some have used unbiased stereology to estimate their numbers (Chadi et al., 1993; Liberatore et al., 1999; Walters et al., 1999).”
BackgroundMethodReactive Nitrogen Species: Molecular Mechanisms and Potential Significance in Health and Disease
Martínez, M. C., & Andriantsitohaina, R. (2008) · Antioxidants and Redox Signaling · doi:10.1089/ars.2007.1993 · Cited by 329 · see citing works
“RNS-dependent mechanisms contribute to neurodegeneration in Parkinson’s disease, as shown by the increased expression of iNOS in Parkinson experimental models associated with dopaminergic neuronal loss (178, 237).”
Novel anti-inflammatory therapy for Parkinson's disease
Gao, H., Liu, B., Zhang, W., & Hong, J. (2003) · Trends in Pharmacological Sciences · doi:10.1016/s0165-6147(03)00176-7 · Cited by 324 · see citing works
Therapeutic immunization protects dopaminergic neurons in a mouse model of Parkinson's disease
Benner, E. J., Mosley, R. L., Destache, C. J., Lewis, T. B., Jackson-Lewis, V. R., Gorantla, S., Nemachek, C., Green, S. R., Przedborski, S., & Gendelman, H. E. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0400569101 · Cited by 321 · see citing works
Self-citationSelective microglial activation in the rat rotenone model of Parkinson's disease
Sherer, T., Betarbet, R. S., Kim, J.-H., & Greenamyre, J. T. (2003) · Neuroscience Letters · doi:10.1016/s0304-3940(03)00172-1 · Cited by 317 · see citing works
HENEKA, M., & LANDRETH, G. (2007) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2007.04.016 · Cited by 317 · see citing works
Chronic stress and glucocorticoids: From neuronal plasticity to neurodegeneration
Vyas, S., Rodrigues, A. J., Silva, J. M., Tronche, F., Almeida, O. F. X., Sousa, N., & Sotiropoulos, I. (2016) · Neural Plasticity · doi:10.1155/2016/6391686 · Cited by 297 · see citing works
Drechsel, D. A., & Patel, M. (2008) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2008.02.008 · Cited by 314 · see citing works
Involvement of Interferon-γ in Microglial-Mediated Loss of Dopaminergic Neurons
Mount, M. P., Lira, A., Grimes, D., Smith, P. D., Faucher, S., Slack, R. S., Anisman, H., Hayley, S. P., & Park, D. S. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.5321-06.2007 · Cited by 316 · see citing works
“This notion is supported by the fact that MPTP (MPP metabolite) can directly target mitochondria in neurons and lead to increased ROS and damage (Liberatore et al., 1999; Dehmer et al., 2000; Gonzalez-Polo et al., 2004; Chen et al., 2006).”
BackgroundGlutathione—a review on its role and significance in Parkinson's disease
Martin, H. L., & Teismann, P. (2009) · The FASEB Journal · doi:10.1096/fj.08-125443 · Cited by 314 · see citing works
An inflammatory review of Parkinson's disease
Orr, C. F., Rowe, D. B., & Halliday, G. M. (2002) · Progress in Neurobiology · doi:10.1016/s0301-0082(02)00127-2 · Cited by 309 · see citing works
Microglial phenotypes in Parkinson’s disease and animal models of the disease
Joers, V., Tansey, M. G., Mulas, G., & Carta, A. R. (2017) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2016.04.006 · Cited by 285 · see citing works
“An increase of mRNA and protein for inflammatory cytokines, such as IL-1β, TNF and IL-6, has been consistently reported after acute MPTP exposure together with an increase of inducible nitric oxide synthase (iNOS) levels, suggesting that reactive microglia acquired an early pro-inflammatory phenotype in this model (Bi…”
BackgroundJones, K. L., & Barr, G. A. (2000) · Synapse · doi:10.1002/1098-2396(200102)39:2 · Cited by 11 · see citing works
Gao, H., Liu, B., Zhang, W., & Hong, J. (2003) · The FASEB Journal · doi:10.1096/fj.03-0109fje · Cited by 306 · see citing works
“Recent reports indicate that glia participate in MPTP-induced dopaminergic neurodegeneration in the rodent PD model (10, 11, 14, 15, 26).”
BackgroundInfluentialNeuroinflammation and oxidative stress: Co-conspirators in the pathology of Parkinson’s disease
Taylor, J. M., Main, B. S., & Crack, P. J. (2013) · Neurochemistry International · doi:10.1016/j.neuint.2012.12.016 · Cited by 303 · see citing works
“Increased levels of iNOS have also been reported in mice injected with MPTP, while mice lacking the gene for iNOS display protection against MPTP-induced DA degeneration (Liberatore et al., 1999).”
BackgroundNeuroglia in neurodegeneration
Heneka, M. T., Rodriguez, J. J., & Verkhratsky, A. (2009) · Brain Research Reviews · doi:10.1016/j.brainresrev.2009.11.004 · Cited by 303 · see citing works
Oxidative and nitrosative stress in Parkinson's disease
Tsang, A. H. K., & Chung, K. K. K. (2009) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2008.12.006 · Cited by 300 · see citing works
“This pathogenic mechanism has been verified in iNOS and nNOS knock out mice in which these animals are resistant to MPTP induced toxicity [106, 107].”
BackgroundAstrogliosis in CNS Pathologies: Is There A Role for Microglia?
Zhang, D., Hu, X., Li, Q., O'Callaghan, J. P., & Hong, J. (2010) · Molecular Neurobiology · doi:10.1007/s12035-010-8098-4 · Cited by 295 · see citing works
“In MPTP-induced neuropathological damage in mice, activation of microglia peaked at 2 days and activation of astrocyte peaked at 4 days after injection [83].”
Neuroinflammatory processes in Parkinson's disease
Hirsch, É. C., Hunot, S., & Hartmann, A. (2005) · Parkinsonism & Related Disorders · doi:10.1016/j.parkreldis.2004.10.013 · Cited by 298 · see citing works
“[39] Liberatore GT, JacksonLewis V, Vukosavic S, Mandir AS, Vila M,”
BackgroundResultInfluentialThe influence of microglia on the pathogenesis of Parkinson's disease
Long-Smith, C. M., Sullivan, A. M., & Nolan, Y. M. (2009) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2009.08.001 · Cited by 296 · see citing works
Cell death pathways in Parkinson’s disease: proximal triggers, distal effectors, and final steps
Levy, O. A., Malagelada, C., & Greene, L. A. (2009) · APOPTOSIS · doi:10.1007/s10495-008-0309-3 · Cited by 287 · see citing works
“NADPH oxidase or iNOS null mice have less nigral cell loss and less oxidative damage in response to MPTP [153, 182].”
Przedborski, S., & Vila, M. (2003) · PubMed · Cited by 286 · see citing works
Self-citationChoi, D., Pennathur, S., Perier, C., Tieu, K., Teismann, P., Wu, D.-C., Jackson-Lewis, V. R., Vila, M., Vonsattel, J., Heinecke, J. W., et al. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.0970-05.2005 · Cited by 284 · see citing works
“However, epidemiological studies suggest that inflammation increases the risk of developing PD (Chen et al., 2003), and experimental models of PD show that inflammatory oxidants modulate SNpc dopaminergic neuronal death (Liberatore et al., 1999; Gao et al., 2002; Wu et al., 2002, 2003).”
BackgroundInfluentialSelf-citation
- 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 › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › 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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