Protection by the NDI1 gene against neurodegeneration in a rotenone rat model of Parkinson's disease
Open accessAbstract
It is widely recognized that mitochondrial dysfunction, most notably defects in the NADH-quinone oxidoreductase (complex I), is closely related to the etiology of sporadic Parkinson's disease (PD). In fact, rotenone, a complex I inhibitor, has been used for establishing PD models both in vitro and in vivo. A rat model with chronic rotenone exposure seems to reproduce pathophysiological conditions of PD more closely than acute mouse models as manifested by neuronal cell death in the substantia nigra and Lewy body-like cytosolic aggregations. Using the rotenone rat model, we investigated the protective effects of alternative NADH dehydrogenase (Ndi1) which we previously demonstrated to act as a replacement for complex I both in vitro and in vivo. A single, unilateral injection of recombinant adeno-associated virus carrying the NDI1 gene into the vicinity of the substantia nigra resulted in expression of the Ndi1 protein in the entire substantia nigra of that side. It was clear that the introduction of the Ndi1 protein in the substantia nigra rendered resistance to the deleterious effects caused by rotenone exposure as assessed by the levels of tyrosine hydroxylase and dopamine. The presence of the Ndi1 protein also prevented cell death and oxidative damage to DNA in dopaminergic neurons observed in rotenone-treated rats. Unilateral protection also led to uni-directional rotation of the rotenone-exposed rats in the behavioral test. The present study shows, for the first time, the powerful neuroprotective effect offered by the Ndi1 enzyme in a rotenone rat model of PD.
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Ndi1 protects against neurodegeneration in rats fed MPTP.
“and also protect against neurodegeneration in rats fed with MPTP, a hallucinogen known to cause a form of Parkinson's disease (PD) [245].”
From Mitochondrial DNA mutations and human disease (2010) · cites this paper as [245]
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Cites
Abràmoff, M. D., Magalhães, P. J., & Ram, S. J. (2004) · Utrecht University Repository (Utrecht University) · Cited by 11,816 · see citing works
Chronic Parkinsonism in Humans Due to a Product of Meperidine-Analog Synthesis
Langston, J. W., Ballard, P., Tetrud, J. W., & Irwin, I. (1983) · Science · doi:10.1126/science.6823561 · Cited by 4,914 · see citing works
Chronic systemic pesticide exposure reproduces features of Parkinson's disease
Betarbet, R., Sherer, T., Mackenzie, G., Garcia-Osuna, M., Panov, A., & Greenamyre, J. (2000) · Nature Neuroscience · doi:10.1038/81834 · Cited by 3,797 · see citing works
Self-citationLanger, R. (1990) · Science · doi:10.1126/science.2218494 · Cited by 1,778 · see citing works
Incidence of Parkinson's Disease: Variation by Age, Gender, and Race/Ethnicity
Eeden, S. K. V. D. (2003) · American Journal of Epidemiology · doi:10.1093/aje/kwg068 · Cited by 1,746 · see citing works
Role of Quinones in Toxicology
Bolton, J. L., Trush, M. A., Penning, T. M., Dryhurst, G., & Monks, T. J. (2000) · Chemical Research in Toxicology · doi:10.1021/tx9902082 · Cited by 1,703 · see citing works
MOLECULAR PATHOPHYSIOLOGY OF PARKINSON'S DISEASE
Moore, D. J., West, A. B., Dawson, V. L., & Dawson, T. M. (2005) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.28.061604.135718 · Cited by 1,274 · see citing works
Mechanism of Toxicity in Rotenone Models of Parkinson's Disease
Sherer, T., Betarbet, R. S., Testa, C. M., Seo, B. B., Richardson, J. R., Kim, J. H., Miller, G. W., Yagi, T., Matsuno‐Yagi, A., & Greenamyre, J. T. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-34-10756.2003 · Cited by 1,073 · see citing works
Self-citationKußmaul, L., & Hirst, J. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0510977103 · Cited by 720 · see citing works
Sherer, T., Kim, J.-H., Betarbet, R. S., & Greenamyre, J. T. (2002) · Experimental Neurology · doi:10.1006/exnr.2002.8072 · Cited by 707 · see citing works
Self-citationDiagnosis and treatment of Parkinson disease: molecules to medicine
Savitt, J. M. (2006) · Journal of Clinical Investigation · doi:10.1172/jci29178 · Cited by 649 · see citing works
PYCOCK, C. (1980) · Neuroscience · doi:10.1016/0306-4522(80)90048-2 · Cited by 610 · see citing works
Rotenone destroys dopaminergic neurons and induces parkinsonian symptoms in rats
Alam, M., & Schmidt, W. (2002) · Behavioural Brain Research · doi:10.1016/s0166-4328(02)00180-8 · Cited by 475 · see citing works
Animal Models of Action Tremor
Elble, R. J. (2008) · Movement Disorders · doi:10.1002/mds.870131306 · Cited by 381 · see citing works
Betarbet, R. S., Canet-Aviles, R., Sherer, T., Mastroberardino, P. G., McLendon, C., Kim, J.-H., Lund, S. A., Na, H. M., Taylor, G., Bence, N., et al. (2006) · Neurobiology of Disease · doi:10.1016/j.nbd.2005.12.003 · Cited by 342 · see citing works
Self-citationPetroske, 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
MPTP mechanisms of neurotoxicity and their implications for Parkinson's disease
Gerlach, M., Riederer, P. F., Przuntek, H., & Youdim, M. B. H. (1991) · European Journal of Pharmacology Molecular Pharmacology · doi:10.1016/0922-4106(91)90073-q · Cited by 307 · see citing works
New Insights into Type II NAD(P)H:Quinone Oxidoreductases
Melo, A. M. P., Bandeiras, T. M., & Teixeira, M. S. (2004) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.68.4.603-616.2004 · Cited by 270 · see citing works
Champy, P., Höglinger, G. U., Féger, J., Gleye, C., Hocquemiller, R., Laurens, A., Guérineau, V., Laprévôte, O., Medja, F., Lombès, A., et al. (2003) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2003.02138.x · Cited by 254 · see citing works
Annonacin, a Natural Mitochondrial Complex I Inhibitor, Causes Tau Pathology in Cultured Neurons
Escobar-Khondiker, M., Höllerhage, M., Muriel, M., Champy, P., Bach, A., Depienne, C., Respondek, G., Yamada, E. S., Lannuzel, A., Yagi, T., et al. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.1644-07.2007 · Cited by 212 · see citing works
Self-citationSeo, B. B., Kitajima‐Ihara, T., Chan, E. K. L., Scheffler, I. E., Matsuno‐Yagi, A., & Yagi, T. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.16.9167 · Cited by 187 · see citing works
Self-citationCrossroads in GDNF therapy for Parkinson's disease
Sherer, T., Fiske, B. K., Svendsen, C. N., Lang, A. E., & Langston, J. W. (2006) · Movement Disorders · doi:10.1002/mds.20861 · Cited by 172 · see citing works
Bashkatova, V. G., Alam, M., Vanin, A. F., & Schmidt, W. (2004) · Experimental Neurology · doi:10.1016/j.expneurol.2003.12.005 · Cited by 127 · see citing works
Jicha, G. A., Berenfeld, B., & Davies, P. (1999) · Journal of Neuroscience Research · doi:10.1002/(sici)1097-4547(19990315)55:6 · Cited by 123 · see citing works
Richardson, J. R., Caudle, W. M., Guillot, T. S., Watson, J. L., Nakamaru‐Ogiso, E., Seo, B. B., Sherer, T., Greenamyre, J. T., Yagi, T., Matsuno‐Yagi, A., et al. (2006) · Toxicological Sciences · doi:10.1093/toxsci/kfl133 · Cited by 117 · see citing works
Self-citationRecombinant Adeno-Associated Viral Vectors in the Nervous System
Burger, C., Nash, K., & Mandel, R. J. (2005) · Human Gene Therapy · doi:10.1089/hum.2005.16.781 · Cited by 110 · see citing works
Respiration in Archaea and Bacteria
(2004) · Advances in photosynthesis and respiration · doi:10.1007/978-1-4020-3163-2 · Cited by 110 · see citing works
Waldmeier, P. C., Bozyczko‐Coyne, D., Williams, M. J., & Vaught, J. L. (2006) · Biochemical Pharmacology · doi:10.1016/j.bcp.2006.06.031 · Cited by 95 · see citing works
The single subunit NADH dehydrogenase reduces generation of reactive oxygen species from complex I
Seo, B. B., Marella, M., Yagi, T., & Matsuno‐Yagi, A. (2006) · FEBS Letters · doi:10.1016/j.febslet.2006.10.008 · Cited by 89 · see citing works
Self-citationMechanism of Cell Death Caused by Complex I Defects in a Rat Dopaminergic Cell Line
Marella, M., Seo, B. B., Matsuno‐Yagi, A., & Yagi, T. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m701819200 · Cited by 87 · see citing works
Self-citationIn Vivo Complementation of Complex I by the Yeast Ndi1 Enzyme
Seo, B. B., Nakamaru‐Ogiso, E., Flotte, T. R., Matsuno‐Yagi, A., & Yagi, T. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m600922200 · Cited by 83 · see citing works
Self-citationSeo, B. B., Wang, J., Flotte, T. R., Yagi, T., & Matsuno‐Yagi, A. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m007033200 · Cited by 75 · see citing works
Self-citationSeo, B. B., Matsuno‐Yagi, A., & Yagi, T. (1999) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/s0005-2728(99)00051-1 · Cited by 66 · see citing works
Self-citationSeo, B. B., Nakamaru‐Ogiso, E., Flotte, T. R., et al. (2002) · Molecular Therapy · doi:10.1006/mthe.2002.0674 · Cited by 51 · see citing works
Self-citationPark, J. S., Li, Y.-F., & Bai, Y. (2007) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2007.01.009 · Cited by 47 · see citing works
An update on the treatment of Parkinson's disease.
Jankovic, J. J. (2006) · PubMed · Cited by 45 · see citing works
Seo, B. B., Nakamaru‐Ogiso, E., Cruz, P. E., et al. (2004) · Human Gene Therapy · doi:10.1089/hum.2004.15.887 · Cited by 40 · see citing works
Self-citationA delivery strategy for rotenone microspheres in an animal model of Parkinson's disease
Huang, J., Liu, H., Gu, W., Yan, Z., Xu, Z., Yang, Y., Zhu, X., & Li, Y. (2005) · Biomaterials · doi:10.1016/j.biomaterials.2005.07.005 · Cited by 35 · see citing works
From Drugs of Abuse to Parkinsonism: The MPTP Mouse Model of Parkinson's Disease
Lau, Y., & Meredith, G. E. (2003) · Humana Press eBooks · doi:10.1385/1-59259-358-5:103 · Cited by 15 · see citing works
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Research works printed but not linked: 1
- [11]Przedborski S Jackson-Lewis V 1998 Mechanisms of MPTP toxicity. Mov Disord 13 Suppl 1 35 8 9613716
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Sorted by citations
Mitochondrial DNA mutations and human disease
Tuppen, H. A. L., Blakely, E. L., Turnbull, D. M., & Taylor, R. W. (2010) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2009.09.005 · Cited by 676 · see citing works
“Mitochondrial targeting of the S.cerevisiae single subunit NADH oxidase, Ndi1, has been shown to rescue complex I de fi ciency in human cells [244] and also protect against neurodegeneration in rats fed with MPTP, a hallucinogen known to cause a form of Parkinson's disease (PD) [245].”
BackgroundMitochondrial respiratory complex I: Structure, function and implication in human diseases
Sharma, L., Lu, J., & Bai, Y. (2009) · Current Medicinal Chemistry · doi:10.2174/092986709787846578 · Cited by 438 · see citing works
Choi, W.-S., Palmiter, R. D., & Xia, Z. (2011) · Journal of Cell Biology · doi:10.1083/jcb.201009132 · Cited by 183 · see citing works
Youn, J. Y., Gao, L., & Cai, H. (2012) · Diabetologia · doi:10.1007/s00125-012-2557-6 · Cited by 128 · see citing works
Progress and prospects: gene therapy for mitochondrial DNA disease
Kyriakouli, D. S., Boesch, P., Taylor, R. W., & Lightowlers, R. N. (2008) · Gene Therapy · doi:10.1038/gt.2008.91 · Cited by 76 · see citing works
- Authors
- Marella, M., Seo, B. B., Nakamaru-Ogiso, E., Greenamyre, J. T., Matsuno-Yagi, A., & Yagi, T.
- Affiliations
- Scripps Research Institute (US)
- University of Pittsburgh (US)
- Corresponding author
- Yagi, Takao
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2008-01-16
- Volume
- 3
- Issue
- 1
- Pages
- e1433
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC2175531
- OpenAlex
- W2009294443
- Cited by
- 116
- References
- 39
- Citations by year
- 2026: 1 · 2025: 6 · 2024: 3 · 2023: 9 · 2022: 3 · 2021: 1 · 2020: 1 · 2019: 3 · 2018: 5 · 2017: 4 · 2016: 7 · 2015: 9 · 2014: 9 · 2013: 8 · 2012: 11
- FWCI
- 7.70
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- D-Scholarship@Pitt (University of Pittsburgh) (acceptedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Funders
- U.S. Public Health Service
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK053244)
- National Institute of Neurological Disorders and Stroke (R01NS048441)
- National Institute of Environmental Health Sciences (U54ES012068)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Coenzyme Q10 studies and effects
- Keywords
- NDI1, NADH dehydrogenase, Parkinson's disease, rotenone, neuroprotection, complex I deficiency, mitochondrial dysfunction, substantia nigra, dopaminergic neurons, AAV gene delivery, tyrosine hydroxylase, dopamine, oxidative DNA damage, rotational behavior
- MeSH terms
- Animals, Behavior, Animal, Dopamine, Male, NADH Dehydrogenase, Rotenone, Substantia Nigra, Rats, Sprague-Dawley, Parkinsonian Disorders, Rats
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