BRAIN, SKELETAL MUSCLE AND PLATELET HOMOGENATE MITOCHONDRIAL FUNCTION IN PARKINSON'S DISEASE
Abstract
The recent discovery of mitochondrial complex I deficiency in the substantia nigra of patients with idiopathic Parkinson's disease has provided new understanding into the possible mechanisms that may underlie this neurodegenerative disorder. The biochemical defect is identical to that induced in humans, primates and mice exposed to the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. We have studied mitochondrial respiratory chain function in various brain regions, in skeletal muscle and in blood platelets from patients with idiopathic Parkinson's disease and from matched controls. We provide evidence suggesting that the complex I deficiency in Parkinson's disease is limited to the brain and that this defect is specific for the substantia nigra. The tissue specificity of the complex I deficiency in Parkinson's disease and its localization to the substantia nigra support the proposition that complex I deficiency may be directly involved in the cause of dopaminergic cell death in Parkinson's disease. An understanding of the molecular basis of this biochemical defect will provide valuable insight into the cause of Parkinson's disease. Our findings of normal mitochondrial function in platelet homogenates suggests that this tissue cannot be used to develop a 'diagnostic test' for Parkinson's disease.
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Impairment of mitochondrial complex-I activity has been observed in the substantia nigra, platelets, and skeletal muscle of PD patients, in some but not all studies.
“An impairment of mitochondrial complex-I activity has been observed in the substantia nigra (SN), platelets, and skeletal muscle of PD patients 1, 9-13, in some but not in all studies14, 15.”
From Mitochondrial Approaches for Neuroprotection (2008) · cites this paper as [14]
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Lang, A. E., & Lozano, A. M. (1998) · New England Journal of Medicine · doi:10.1056/nejm199810083391506 · Cited by 2,041 · see citing works
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“was tissue and disease specific, although also detectable in platelets and muscle in PD [85,129,130,132].”
BackgroundSherer, 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
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Winklhofer, K. F., & Haass, C. (2010) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2009.08.013 · Cited by 688 · see citing works
Berman, S. B., & Hastings, T. G. (1999) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1999.0731127.x · Cited by 664 · see citing works
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Do defecs in mitochondrial energy metabolism underlie the pathology of neurodegenerative diseases?
Beal, M. F., Hyman, B. T., & Koroshetz, W. J. (1993) · Trends in Neurosciences · doi:10.1016/0166-2236(93)90117-5 · Cited by 574 · see citing works
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Gegg, M. E., Burke, D., Heales, S., Cooper, J., Hardy, J., Wood, N., & Schapira, A. (2012) · Annals of Neurology · doi:10.1002/ana.23614 · Cited by 551 · see citing works
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Beal, M. F. (2003) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2003.tb07470.x · Cited by 523 · see citing works
Oxidative stress: Free radical production in neural degeneration
Götz, M. E., Künig, G., Riederer, P. F., & Youdim, M. B. H. (1994) · Pharmacology & Therapeutics · doi:10.1016/0163-7258(94)90055-8 · Cited by 479 · see citing works
Energetics in the pathogenesis of neurodegenerative diseases
Beal, M. F. (2000) · Trends in Neurosciences · doi:10.1016/s0166-2236(00)01584-8 · Cited by 472 · see citing works
The pathogenesis of cell death in Parkinson's disease
Jenner, P. G., & Olanow, C. W. (2006) · Neurology · doi:10.1212/wnl.66.10_suppl_4.s24 · Cited by 449 · see citing works
Haas, R. H., Nasirian, F., Nakano, K., Ward, D., Pay, M., Hill, R., & Shults, C. W. (1995) · Annals of Neurology · doi:10.1002/ana.410370604 · Cited by 435 · see citing works
Mitochondrial Diseases of the Brain
Chaturvedi, R. K., & Beal, M. F. (2013) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2013.03.018 · Cited by 416 · see citing works
“Impairment of mitochondrial complex activity is not only restricted to the brain but also reported to be decreased in peripheral tissues such as skeletal muscle, lymphocytes and platelets of PD patients[28–35].”
BackgroundMitochondrial dysfunction in Parkinson’s disease – a key disease hallmark with therapeutic potential
Henrich, M. T., Oertel, W. H., Surmeier, D. J., & Geibl, F. F. (2023) · Molecular Neurodegeneration · doi:10.1186/s13024-023-00676-7 · Cited by 435 · see citing works
Increased levels of lipid hydroperoxides in the parkinsonian substantia nigra: An HPLC and ESR study
Dexter, D. T., Holley, A. E., Flitter, W. D., Slater, T. F., Wells, F. R., Daniel, S. E., Lees, A. J., Jenner, P. G., & MARSDEN, C. D. (1994) · Movement Disorders · doi:10.1002/mds.870090115 · Cited by 407 · see citing works
Self-citationJung, T., Catalgol, B., & Grune, T. (2009) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2009.04.001 · Cited by 389 · see citing works
Complex I deficiency in Parkinson's disease frontal cortex
Parker, W. D., Parks, J. K., & Swerdlow, R. H. (2007) · Brain Research · doi:10.1016/j.brainres.2007.10.061 · Cited by 383 · see citing works
Loss of the Parkinson's disease-linked gene DJ-1 perturbs mitochondrial dynamics
Irrcher, I., Aleyasin, H., Seifert, E. L., Hewitt, S. J., Chhabra, S., Phillips, M., Lutz, A. K., Rousseaux, M. W. C., Bevilacqua, L., Jahani‐Asl, A., et al. (2010) · Human Molecular Genetics · doi:10.1093/hmg/ddq288 · Cited by 386 · see citing works
Cassarino, D. S., & Bennett, J. P. (1999) · Brain Research Reviews · doi:10.1016/s0165-0173(98)00046-0 · Cited by 379 · see citing works
Monzio Compagnoni, G., Di Fonzo, A., Corti, S., Comi, G. P., Bresolin, N., & Masliah, E. (2020) · Molecular Neurobiology · doi:10.1007/s12035-020-01926-1 · Cited by 378 · see citing works
Bioenergetic and oxidative stress in neurodegenerative diseases
Bowling, A. C., & Beal, M. F. (1995) · Life Sciences · doi:10.1016/0024-3205(95)00055-b · Cited by 364 · see citing works
Platelet mitochondria function in Parkinson's disease
Krige, D., Carroll, M. T., Cooper, J. A. D., MARSDEN, C. D., & Schapira, A. H. V. (1992) · Annals of Neurology · doi:10.1002/ana.410320612 · Cited by 358 · see citing works
Self-citationCooper, J. A. D., Mann, V. M., & Schapira, A. H. V. (1992) · Journal of the Neurological Sciences · doi:10.1016/0022-510x(92)90270-u · Cited by 335 · see citing works
Self-citationChronic systemic complex I inhibition induces a hypokinetic multisystem degeneration in rats
Höglinger, G. U., Féger, J., Prigent, A., Michel, P. P., Parain, K., Champy, P., Ruberg, M., Oertel, W. H., & Hirsch, É. C. (2003) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2003.01533.x · Cited by 331 · see citing works
The mitochondrial transcription factor TFAM in neurodegeneration: emerging evidence and mechanisms
Kang, I., Chu, C. T., & Kaufman, B. A. (2018) · FEBS Letters · doi:10.1002/1873-3468.12989 · Cited by 325 · see citing works
Dexter, D. T., Sian, J., Rose, S., Hindmarsh, J. G., Mann, V. M., Cooper, J. A. D., Wells, F. R., Daniel, S. E., Lees, A. J., Schapira, A. H. V., et al. (1994) · Annals of Neurology · doi:10.1002/ana.410350107 · Cited by 317 · see citing works
Self-citationSchapira, A. H. V. (1999) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/s0005-2728(98)00164-9 · Cited by 310 · see citing works
Self-citationJones, K. L., & Barr, G. A. (2000) · Synapse · doi:10.1002/1098-2396(200102)39:2 · Cited by 11 · see citing works
Cassarino, D. S., Parks, J. K., Parker, W. D., & Bennett, J. P. (1999) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/s0925-4439(98)00083-0 · Cited by 304 · see citing works
Redox imbalance in Parkinson's disease
Chinta, S. J., & Andersen, J. K. (2008) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2008.02.005 · Cited by 302 · see citing works
Glutathione‐related enzymes in brain in Parkinson's disease
Sian, J., Dexter, D. T., Lees, A. J., Daniel, S. E., Jenner, P. G., & MARSDEN, C. D. (1994) · Annals of Neurology · doi:10.1002/ana.410360306 · Cited by 296 · see citing works
Self-citationMitochondrial Approaches for Neuroprotection
Chaturvedi, R. K., & Beal, M. F. (2008) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1427.027 · Cited by 294 · see citing works
Benzi, G., & Moretti, A. (1995) · Free Radical Biology and Medicine · doi:10.1016/0891-5849(94)00244-e · Cited by 283 · see citing works
Beal, M. F. (2004) · Journal of Bioenergetics and Biomembranes · doi:10.1023/b:jobb.0000041772.74810.92 · Cited by 276 · see citing works
Parkin enhances mitochondrial biogenesis in proliferating cells
Kuroda, Y., Mitsui, T., Kunishige, M., Shono, M., Akaike, M., Azuma, H., & Matsumoto, T. (2006) · Human Molecular Genetics · doi:10.1093/hmg/ddl006 · Cited by 268 · see citing works
“mitochondrial complex I deficiency seems responsible for the nigral degeneration (6,7).”
BackgroundUnexpected expression of α- and β-globin in mesencephalic dopaminergic neurons and glial cells
Biagioli, M., Pinto, M., Cesselli, D., Zaninello, M., Lazarević, D., Roncaglia, P., Simone, R., Vlachouli, C., Plessy, C., Bertin, N., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0813216106 · Cited by 261 · see citing works
“Complex I plays a central role in PD because deficits in its subunits and activity have been consistently detected in the SN of PD patients (32).”
BackgroundCassarino, D. S., Fall, C. P., Swerdlow, R. H., Smith, T. S., Halvorsen, E. M., Miller, S. W., Parks, J. K., Parker, W. D., & Bennett, J. P. (1997) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/s0925-4439(97)00070-7 · Cited by 265 · see citing works
Inden, M., Kitamura, Y., Takeuchi, H., Yanagida, T., Takata, K., Kobayashi, Y., Taniguchi, T., Yoshimoto, K., Kaneko, M., Okuma, Y., et al. (2007) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2006.04440.x · Cited by 261 · see citing works
Zhang‐James, Y., James, M., Middleton, F. A., & Davis, R. L. (2005) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30195 · Cited by 261 · see citing works
“…in idiopathic PD. Complex I activity and the reduced form of glutathione are diminished in the SNpc of PD patients, resulting in impaired oxidative phosphorylation, increased electron leakage and free radical production, and reduced clearance of H2O2 [Schapira et al., 1989; Mann et al., 1992].”
BackgroundInfluentialMitochondrial dysfunction in the limelight of Parkinson's disease pathogenesis
Banerjee, R., Starkov, A. A., Beal, M. F., & Thomas, B. (2008) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2008.11.007 · Cited by 256 · see citing works
“Several studies showed impaired complex I, II+III, and IV in PD muscle [39–41], whereas others reported no differences [29,42,43], and findings on the ETC deficiency in PD lymphocytes [20,44] are counter-balanced by the evidence on the absence of such deficiencies [45].”
BackgroundResultComplex I, iron, and ferritin in Parkinson's disease substantia nigra
Mann, V. M., Cooper, J. M., Daniel, S. E., Srai, K., Jenner, P., Marsden, C. D., & Schapira, A. H. V. (1994) · Annals of Neurology · doi:10.1002/ana.410360612 · Cited by 251 · see citing works
“The finding of a highly statistically significant 32 to 38% decrease in complex I activity in PD presented here extends our previous observations in this area [3].”
BackgroundResultSelf-citationMitochondrial dysfunction in Parkinson's disease
Greenamyre, J. T., MacKenzie, G. M., Peng, T., & Stephans, S. E. (1999) · Biochemical Society Symposia · doi:10.1042/bss0660085 · Cited by 248 · see citing works
Bioenergetics and glutamate excitotoxicity
Greene, J. G., & Greenamyre, J. T. (1996) · Progress in Neurobiology · doi:10.1016/0301-0082(96)00006-8 · Cited by 246 · see citing works
Brain mitochondrial dysfunction in aging
Boveris, A., & Navarro, A. (2008) · IUBMB Life · doi:10.1002/iub.46 · Cited by 235 · see citing works
“Decreased complex IV activity has been reported in Alzheimer’s disease (41) and decreased complex I activity is usually reported in the substantia nigra of postmorten samples (42, 43).”
BackgroundHolper, L., Ben‐Shachar, D., & Mann, J. (2018) · Neuropsychopharmacology · doi:10.1038/s41386-018-0090-0 · Cited by 234 · see citing works
Merad-Boudia, M., Nicole, A., Santiard-Baron, D., Saillé, C., & Ceballos-Picot, I. (1998) · Biochemical Pharmacology · doi:10.1016/s0006-2952(97)00647-3 · Cited by 227 · see citing works
Contributory mechanisms in the causation of neurodegenerative disorders
Lees, G. J. (1993) · Neuroscience · doi:10.1016/0306-4522(93)90254-d · Cited by 221 · see citing works
Macdonald, R., Barnes, K., Hastings, C., & Mortiboys, H. (2018) · Biochemical Society Transactions · doi:10.1042/bst20170501 · Cited by 216 · see citing works
Evidence for mitochondrial dysfunction in Parkinson's disease—a critical appraisal
Schapira, A. H. V. (1994) · Movement Disorders · doi:10.1002/mds.870090202 · Cited by 218 · see citing works
Self-citationGlutathione and Parkinson's disease: Is this the elephant in the room?
Zeevalk, G. D., Razmpour, R., & Bernard, L. P. (2008) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2008.01.017 · Cited by 209 · see citing works
Mitochondrial dysfunction, oxidative stress and neurodegeneration
Mancuso, M., Coppedè, F., Migliore, L., Siciliano, G., & Murri, L. (2006) · Journal of Alzheimer s Disease · doi:10.3233/jad-2006-10110 · Cited by 209 · see citing works
“In skeletal muscle of PD patients, reduced complex I activity was observed by some groups [14], but denied by others [94].”
Mitochondrial dysfunction in neurodegenerative disorders
Schapira, A. H. V. (1998) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/s0005-2728(98)00115-7 · Cited by 210 · see citing works
Self-citationWang, X., Petrie, T. G., Liu, Y., Liu, J., Fujioka, H., & Zhu, X. (2012) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2012.07734.x · Cited by 206 · see citing works
α-Synuclein: Normal Function and Role in Neurodegenerative Diseases
Norris, E. H., Giasson, B. I., & Lee, V. M. ‐. (2004) · Current topics in developmental biology/Current Topics in Developmental Biology · doi:10.1016/s0070-2153(04)60002-0 · Cited by 202 · see citing works
An immunohistochemical study on α‐ketoglutarate dehydrogenase complex in Parkinson's disease
Mizuno, Y., Matuda, S., Yoshino, H., Mori, H., Hattori, N., & Ikebe, S. (1994) · Annals of Neurology · doi:10.1002/ana.410350212 · Cited by 199 · see citing works
Initiation of Neuronal Damage by Complex I Deficiency and Oxidative Stress in Parkinson's Disease
Tretter, L., Sipos, I., & Ádám‐Vizi, V. (2004) · Neurochemical Research · doi:10.1023/b:nere.0000014827.94562.4b · Cited by 199 · see citing works
“deficiency both in the brain (14–16) and in peripheral tissues (17,18).”
BackgroundParkinson's disease and anaesthesia
Nicholson, G., Pereira, A. C., & Hall, G. M. (2002) · British Journal of Anaesthesia · doi:10.1093/bja/aef268 · Cited by 193 · see citing works
Biomarkers and Parkinson's disease
Michell, A. W. (2004) · Brain · doi:10.1093/brain/awh198 · Cited by 183 · see citing works
“However, there may be a degree of tissue specificity, and at least one study has reported a lack of difference in complex I levels in the platelets of patients with Parkinson’s disease versus controls (Mann et al., 1992), which would limit the ability of peripheral assays to detect central changes.”
BackgroundPlatelet mitochondrial function: from regulation of thrombosis to biomarker of disease.
Zharikov, S. I., & Shiva, S. (2013) · Biochemical Society Transactions · doi:10.1042/bst20120327 · Cited by 182 · see citing works
Blin, O. J., Desnuelle, C., Rascol, O., Borg, M., Paul, H. P. S., Azulay, J., Billé, F., Figarella-Branger, D. F., Coulom, F., Pellissier, J., et al. (1994) · Journal of the Neurological Sciences · doi:10.1016/0022-510x(94)90248-8 · Cited by 182 · see citing works
Role of mitochondria in the etiology and pathogenesis of Parkinson's disease
Mizuno, Y., Ikebe, S., Hattori, N., Nakagawa-Hattori, Y., Mochizuki, H., Tanaka, M., & Ozawa, T. (1995) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/0925-4439(95)00038-6 · Cited by 170 · see citing works
Parkin and PINK1 functions in oxidative stress and neurodegeneration
Barodia, S. K., Creed, R. B., & Goldberg, M. S. (2016) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2016.12.004 · Cited by 168 · see citing works
“…damaged subunits of mitochondrial complex I are increased in PD brains (Keeney et al. 2006) and impaired complex I activity has been observed in multiple tissues and peripheral blood leukocytes from PD patients (Mann et al. 1992; Albers and Beal 2000; Muftuoglu et al. 2004; Schapira 2008).”
BackgroundPerfeito, R., Cunha‐Oliveira, T., & Rego, A. C. (2013) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2013.05.042 · Cited by 165 · see citing works
“Complex I activity and expression are decreased in the SN[109 112] and cortex [113] of PD patients to a greater extent than would be expected from normal aging [107].”
BackgroundMitochondrial function, GSH and iron in neurodegeneration and Lewy body diseases
Gu, M., Owen, A., Toffa, S., Cooper, J. A. D., Dexter, D. T., Jenner, P. G., MARSDEN, C. D., & Schapira, A. H. V. (1998) · Journal of the Neurological Sciences · doi:10.1016/s0022-510x(98)00095-1 · Cited by 164 · see citing works
Self-citationMitochondrial degradation and energy metabolism
Melser, S., Lavie, J., & Bénard, G. (2015) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2015.05.010 · Cited by 163 · see citing works
Mitochondrial DNA mutations in neurodegeneration
Keogh, M. J., & Chinnery, P. F. (2015) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2015.05.015 · Cited by 163 · see citing works
Mitochondrial Dysfunction in Parkinson's Disease
Zhu, J., & Chu, C. T. (2010) · Journal of Alzheimer s Disease · doi:10.3233/jad-2010-100363 · Cited by 158 · see citing works
“Some studies reported that complex I deficiency is only observed in the substantia nigra [16–18] or is more severe in nigral neuronal mitochondria than in platelet mitochondria [19].”
BackgroundBrain mitochondrial dysfunction in aging, neurodegeneration and Parkinson's disease
Navarro, A. (2010) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2010.00034 · Cited by 158 · see citing works
Oxidative Stress and Parkinson's Diseasea
Owen, A., Schapira, A. H. V., Jenner, P. G., & MARSDEN, C. D. (1996) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1996.tb39064.x · Cited by 154 · see citing works
Self-citationGenetics of Parkinson's disease
Nussbaum, R. L. (1997) · Human Molecular Genetics · doi:10.1093/hmg/6.10.1687 · Cited by 155 · see citing works
“Modest deficiencies of complex I of the electron transport chain (reviewed in 2) have been reported in the substantia nigra (21), muscle (37–39) and per ipheral blood cells (39,40) of PD patients but whether these a bnormalities are primary or secondary to the disease process is unknown.”
BackgroundInden, M., Kitamura, Y., Abe, M., Tamaki, A., Takata, K., & Taniguchi, T. (2011) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.34.92 · Cited by 149 · see citing works
MitophAging: Mitophagy in Aging and Disease
Bakula, D., & Scheibye‐Knudsen, M. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00239 · Cited by 150 · see citing works
Kotzbauer, P. T., Truax, A. C., Trojanowski, J. Q., & Lee, V. M. ‐. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.4265-04.2005 · Cited by 148 · see citing works
“Deficits in mitochondrial complex I have been detected in postmortem brain and other tissues in Parkinson’s disease (Bindoff et al., 1989; Parker et al., 1989; Schapira et al., 1990; Shoffner et al., 1991; Mann et al., 1992; Cardellach et al., 1993).”
BackgroundPoint mutations of mitochondrial genome in Parkinson's disease
Ikebe, S.-I., Tanaka, M., & Ozawa, T. (1995) · Molecular Brain Research · doi:10.1016/0169-328x(94)00209-w · Cited by 144 · see citing works
High frequency of mitochondrial complex I mutations in Parkinson’s disease and aging
Smigrodzki, R. M., Parks, J. K., & Parker, W. D. (2004) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2004.02.020 · Cited by 138 · see citing works
Mitochondria and Neurodegeneration
Petrozzi, L., Ricci, G., Giglioli, N. J., Siciliano, G., & Mancuso, M. (2007) · Bioscience Reports · doi:10.1007/s10540-007-9038-z · Cited by 140 · see citing works
“In skeletal muscle of PD patients, reduced complex I activity was observed by some groups (Bindoff et al. 1989), but denied by others (Mann et al. 1992).”
BackgroundM itochondrial DNA and primary mitochondrial dysfunction in P arkinson's disease
Giannoccaro, M. P., Morgia, C. L., Rizzo, G., & Carelli, V. (2017) · Movement Disorders · doi:10.1002/mds.26966 · Cited by 134 · see citing works
“Further issues regarded the biochemical assays methodology, the sensitivity of enzymatic activities to postmortem time and/or tissue conservation, the confounding effect of age-related decline of mitochondrial efficiency, and the possible influence of therapy or cigarette smoking.(39,42,44) Immunoblotting and immuohis…”
BackgroundChomyn, A., Lai, S. T., Shakeley, R. M., Bresolin, N., Scarlato, G., & Attardi, G. M. (1994) · PubMed Central · Cited by 135 · see citing works
Pesticide Exposure Exacerbates α-Synucleinopathy in an A53T Transgenic Mouse Model
Norris, E. H., Uryu, K., Leight, S., Giasson, B. I., Trojanowski, J. Q., & Lee, V. M. ‐. (2007) · American Journal Of Pathology · doi:10.2353/ajpath.2007.060359 · Cited by 134 · see citing works
Mechanistic Approaches to Parkinson's Disease Pathogenesis
Betarbet, R. S., Sherer, T., Monte, D. A. D., & Greenamyre, J. T. (2002) · Brain Pathology · doi:10.1111/j.1750-3639.2002.tb00468.x · Cited by 134 · see citing works
“Later on, reports indicated that the complex I defect is systemic in PD, affecting tissues outside the brain such as platelets, lymphocytes and muscle (8, 10, 15, 62, 69, 71, 84).”
BackgroundTargeting urate to reduce oxidative stress in Parkinson disease
Crotty, G. F., Ascherio, A., & Schwarzschild, M. A. (2017) · Experimental Neurology · doi:10.1016/j.expneurol.2017.06.017 · Cited by 131 · see citing works
“Subsequent studies also found complex I deficiency in the platelets, lymphocytes and skeletal muscle tissues of patients with PD, although this was not consistently seen in skeletal muscle (28,57).”
BackgroundResultCytochrome c Oxidase Deficiency Associated with the First Stop-Codon Point Mutation in Human mtDNA
Hanna, M. G., Nelson, I. P., Rahman, S., et al. (1998) · The American Journal of Human Genetics · doi:10.1086/301910 · Cited by 130 · see citing works
“Polarographic determination of mitochondrial function, spectrophotometric analysis of respiratorychain–enzyme activities, and low-temperature analysis of cytochrome content were performed as described elsewhere (Morgan-Hughes et al. 1977; Mann et al. 1992). mtDNA analysis.”
MethodSelf-citationAhmadi, F. A., Linseman, D. A., Grammatopoulos, T. N., Jones, S. M., Bouchard, R. J., Freed, C. R., Heidenreich, K. A., & Zawada, W. M. (2003) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2003.02068.x · Cited by 127 · see citing works
Apoptotic neuronal death in Parkinson's disease: Involvement of nitric oxide
Singh, S., & Dikshit, M. (2007) · Brain Research Reviews · doi:10.1016/j.brainresrev.2007.02.001 · Cited by 127 · see citing works
Brain mitochondrial dysfunction and oxidative damage in Parkinson’s disease
Navarro, A., & Boveris, A. (2009) · Journal of Bioenergetics and Biomembranes · doi:10.1007/s10863-009-9250-6 · Cited by 126 · see citing works
“Moreover, similar mitochondrial complex I dysfunctions were reported in skeletal muscle and platelets of PD patients (Mann et al. 1992).”
BackgroundFlønes, I. H., Fernández‐Vizarra, E., Lykouri, M., Brakedal, B., SKEIE, G. O., Miletić, H., Lilleng, P. K., Alves, G. W., Tysnes, O., Haugarvoll, K., et al. (2017) · Acta Neuropathologica · doi:10.1007/s00401-017-1794-7 · Cited by 121 · see citing works
“While this phenomenon has been consistently reproduced by multiple studies [17, 18, 23, 24, 34] its significance remains undetermined.”
Członkowska, A., Kurkowska‐Jastrzębska, I., Członkowski, A., Peter, D., & Stefano, G. B. (2002) · PubMed · Cited by 123 · see citing works
Baracca, A., Barogi, S., Carelli, V., Lenaz, G., & Solaini, G. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.6.4177 · Cited by 112 · see citing works
Parkin- and PINK1-Dependent Mitophagy in Neurons: Will the Real Pathway Please Stand Up?
Grenier, K., McLelland, G., & Fon, E. A. (2013) · Frontiers in Neurology · doi:10.3389/fneur.2013.00100 · Cited by 120 · see citing works
“Mitochondrial dysfunction has been a longstanding theme in PD following observations that mitochondrial toxins such as MPTP and rotenone could induce acute parkinsonism (3, 4) and that mitochondrial respiration was defective in the substantia nigra pars compacta (SNpc) of post-mortem PD patients (5).”
BackgroundInfluentialSomatic mitochondrial DNA mutations in cortex and substantia nigra in aging and Parkinson’s disease
Simon, D. K., Lin, M. T., Zheng, L., Liu, G.-J., Ahn, C. H., Kim, L. M., Mauck, W. M., Twu, F., Beal, M. F., & Johns, D. R. (2004) · Neurobiology of Aging · doi:10.1016/s0197-4580(03)00037-x · Cited by 118 · see citing works
“This decline occurs to a greater extent in PD compared to age-matched controls [27,40,52–54].”
ResultKawamata, J., & Shimohama, S. (2011) · Journal of Alzheimer's Disease · doi:10.3233/jad-2011-110173 · Cited by 111 · see citing works
de Sousa, S. C., Maciel, E. N., Vercesi, A. E., & Castilho, R. F. (2003) · FEBS Letters · doi:10.1016/s0014-5793(03)00421-6 · Cited by 109 · see citing works
Omega-3 fatty acids in neurodegenerative diseases: Focus on mitochondria
Eckert, G. P., Lipka, U., & Muller, W. E. (2012) · Prostaglandins Leukotrienes and Essential Fatty Acids · doi:10.1016/j.plefa.2012.05.006 · Cited by 109 · see citing works
- Authors
- MANN, V. M., COOPER, J. M., KRIGE, D., DANIEL, S. E., SCHAPIRA, A. H. V., & MARSDEN, C. D.
- Affiliations
- The Royal Free Hospital (GB)
- Parkinson's UK (GB)
- UCL Queen Square Institute of Neurology (GB)
- Corresponding author
- MANN, V. M.
- Venue
- Brain
- Publisher
- Oxford University Press (OUP)
- Published
- 1992
- Volume
- 115
- Issue
- 2
- Pages
- 333-342
- ISSN
- 0006-8950 (ISSN-L)
- 1460-2156
- OpenAlex
- W2016905315
- Cited by
- 346
- References
- 0
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 2 · 2023: 4 · 2022: 7 · 2021: 6 · 2020: 9 · 2019: 4 · 2018: 11 · 2017: 11 · 2016: 8 · 2015: 10 · 2014: 6 · 2013: 9 · 2012: 14
- FWCI
- 14.96
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Eisai
- Medical Research Council
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Coenzyme Q10 studies and effects
- Keywords
- Parkinson's disease, mitochondrial complex I deficiency, substantia nigra, mitochondrial respiratory chain, MPTP, dopaminergic neuron loss, skeletal muscle mitochondria, platelet mitochondria, tissue specificity, diagnostic testing
- MeSH terms
- Aged, Blood Platelets, Brain, Histocytochemistry, Humans, Middle Aged, Mitochondria, Mitochondria, Muscle, Parkinson Disease
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