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Electron transfer complexes I and IV of platelets are abnormal in Parkinson's disease but normal in Parkinson-plus syndromes
Abstract
Using a technique which requires only 100 ml blood we investigated the electron transfer complexes (ETC) I, III and IV in platelet mitochondria of 44 control subjects, 27 patients with idiopathic Parkinson's disease and eight patients with Parkinson-plus syndromes due to multiple system atrophy. In both control subjects and patients, ETC measurements were repeated at intervals of several months. The activities varied considerably among normal subjects, but intra-individual variation of ETC activities were low at repetitive measurements. In normal subjects there was no correlation between enzyme activities and age or training state. There was no difference in enzyme activities between smokers and non-smokers in the control group. Complex I activity was lower in Parkinson's disease patients than in controls (14 versus 29 nmol/min/mg platelet protein; P < 0.001). Furthermore, the group difference in complex IV activity also reached statistical significance (83 versus 58 nmol/min/mg platelet protein; P < 0.001). Additionally, in some Parkinson's disease patients, activities of complex III were low and lay outside the control range, but the group difference did not reach significance. There was no correlation between complex I activity and disease duration or severity as well as the daily L-dopa dose in Parkinson's disease patients. Repeated measurements in five Parkinson's disease patients in the earliest stages of their illness demonstrated that the decrease in complex I and IV activities can develop rapidly within 1 year. In Parkinson-plus patients suffering from multiple system atrophy the ETC activities were normal.
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“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 [13]
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Shults, C. W. (2002) · Archives of Neurology · doi:10.1001/archneur.59.10.1541 · Cited by 984
Loss of PINK1 causes mitochondrial functional defects and increased sensitivity to oxidative stress
Gautier, C. A., Kitada, T., & Shen, J. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0802076105 · Cited by 698
Mitochondrial dysfunction in Parkinson's disease
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
“Indeed, complex I activities were reported to be significantly reduced (in the range of 30%) in post-mortem substantia nigra of PD patients [44-47], and platelets from PD patients [48-51], while data from skeletal muscle and other non-neuronal tissues are not consistent [52-56].”
BackgroundOrigin and functional consequences of the complex I defect in Parkinson's disease
Swerdlow, R. H., Parks, J. K., Miller, S. W., Davis, R. E., Tuttle, J. B., Trimmer, P. A., Sheehan, J. P., Bennett, J. P., & Parker, W. D. (1996) · Annals of Neurology · doi:10.1002/ana.410400417 · Cited by 638
What Genetics Tells us About the Causes and Mechanisms of Parkinson's Disease
Corti, O., Lesage, S., & Brice, A. (2011) · Physiological Reviews · doi:10.1152/physrev.00022.2010 · Cited by 652
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
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 426
“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].”
BackgroundComplex 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 392
New insights into the complex role of mitochondria in Parkinson’s disease
Grünewald, A., Kumar, K. R., & Sue, C. M. (2018) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2018.09.003 · Cited by 375
“Enzyme kinetic analysis in mitochondria isolated from platelets (Benecke et al., 1993; Krige et al., 1992; Parker et al., 1989) and skeletal muscle (Bindoff et al.”
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
Jin, H., Kanthasamy, A., Ghosh, A., Anantharam, V., Kalyanaraman, B., & Kanthasamy, A. G. (2013) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2013.09.007 · Cited by 373
“Additionally, impairment of complex-I activity has been reported in the substantia nigra, platelets and skeletal muscles of PD patients [85, 86].”
BackgroundShults, C. W., Haas, R. H., Passov, D., & Beal, M. F. (1997) · Annals of Neurology · doi:10.1002/ana.410420221 · Cited by 326
Progression of Parkinson's disease in the clinical phase: potential markers
Maetzler, W., Liepelt, I., & Berg, D. (2009) · The Lancet Neurology · doi:10.1016/s1474-4422(09)70291-1 · Cited by 307
Mitochondrial 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
Beal, M. F., Matthews, R. T., Tieleman, A., & Shults, C. W. (1998) · Brain Research · doi:10.1016/s0006-8993(97)01192-x · Cited by 256
Mitochondrial 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 262
“The activities of other respiratory chain complexes in PD platelets were even more variable, that is some laboratories found impaired complex II [20], complex II + complex III [21], and complex IV activities [22], whereas others reported a selective complex I inhibition [21, 23] (See Table 1 for details).”
BackgroundMitochondrial 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
Zhang, J., Fitsanakis, V. A., Gu, G., Jing, D., Ao, M., Amarnath, V., & Montine, T. J. (2003) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2003.01525.x · Cited by 238
“Although complex I deficiency has been reported in some PD patients, there is evidence to suggest that other mitochondrial complexes are also involved (Benecke et al. 1993; Haas et al. 1995).”
BackgroundInfluentialMitochondrial complex I and IV activities in leukocytes from patients with parkin mutations
Müftüoğlu, M., Elibol, B., Dalmızrak, Ö., Ercan, A., Kulaksiz-Erkmen, G., Öğüş, İ. H., Dalkara, T., & Özer, N. (2003) · Movement Disorders · doi:10.1002/mds.10695 · Cited by 247
Holper, L., Ben‐Shachar, D., & Mann, J. (2018) · Neuropsychopharmacology · doi:10.1038/s41386-018-0090-0 · Cited by 236
Proteomic Identification of a Stress Protein, Mortalin/mthsp70/GRP75
Jin, J., Hulette, C., Wang, Y., Zhang, T., Pan, C., Wadhwa, R., & Zhang, J. (2006) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m500382-mcp200 · Cited by 228
Glutathione 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 217
Role of Platelet Mitochondria: Life in a Nucleus-Free Zone
Melchinger, H., Jain, K., Tyagi, T., & Hwa, J. (2019) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2019.00153 · Cited by 208
“Because mitochondria play such an integral role in platelet metabolism, activation, and apoptosis, it is no surprise that mitochondrial dysfunction contribute to dysfunctional platelet activity and apoptosis in several diseases, most notably Alzheimer’s and Parkinson’s (120), cardiovascular disease (CVD) (121), diabet…”
BackgroundInfluentialResveratrol protects dopaminergic neurons in midbrain slice culture from multiple insults
Okawara, M., Katsuki, H., Kurimoto, E., Shibata, H., Kume, T., & Akaike, A. (2006) · Biochemical Pharmacology · doi:10.1016/j.bcp.2006.11.003 · Cited by 202
“Activities of mitochondrial complexes I and IV are reduced in PD patients [4].”
BackgroundProgress in Parkinson's disease—Where do we stand?
Toulouse, A., & Sullivan, A. M. (2008) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2008.05.003 · Cited by 197
Coenzyme Q10 effects in neurodegenerative disease
Henchcliffe, C. (2009) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s5212 · Cited by 189
“For example, in PD, there is diminished complex I activity in the substantia nigra, platelets, and skeletal muscle,(10,28,42) and reduced activity of both complex I and II/III in platelet mitochondria.(44,45) Moreover, the discovery of multiple PD genes whose function is linked to mitochondrial function or oxidative s…”
Platelet 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
Supramolecular organization of protein complexes in the mitochondrial inner membrane
Vonck, J., & Schäfer, E. (2008) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2008.05.019 · Cited by 168
Poon, H. F., Frasier, M. A., Shreve, N., Calabrese, V., Wolozin, B. L., & Butterfield, D. A. (2005) · Neurobiology of Disease · doi:10.1016/j.nbd.2004.12.009 · Cited by 167
“…impairment of energy production and mitochondrial dysfunction leads to neurodegeneration reminiscent of PD both in in vitro and in vivo studies (Benecke et al., 1993; Bouyer et al., 1984; Marey-Semper et al., 1993; Mizuno et al., 1989; Parker et al., 1989; Shoffner et al., 1991; Zeevalk et…”
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Zhu, J., & Chu, C. T. (2010) · Journal of Alzheimer s Disease · doi:10.3233/jad-2010-100363 · Cited by 160
Sheehan, J. P., Swerdlow, R. H., Parker, W. D., Miller, S. W., Davis, R. E., & Tuttle, J. B. (1997) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1997.68031221.x · Cited by 150
“Purified mitochondria from the platelets of PD patients demonstrate a decrease in complex I (NADH:ubiquinone oxidoreductase) activity of the electron transport chain (ETC) when compared with those of age-matched, disease-free individuals (Parker et al., 1989a; Krige et al., 1992; Benecke et al., 1993; Haas et al., 199…”
ResultSohmiya, M., Tanaka, M., Wei Tak, N., Yanagisawa, M., Tanino, Y., Suzuki, Y., Okamoto, K., & Yamamoto, Y. (2004) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2004.05.007 · Cited by 143
The role of mitochondria in neurodegenerative diseases
Filosto, M., Scarpelli, M., Cotelli, M. S., Vielmi, V., Todeschini, A., Gregorelli, V., Tonin, P., Tomelleri, G., & Padovani, A. (2011) · Journal of Neurology · doi:10.1007/s00415-011-6104-z · Cited by 142
“A reduction in complex I activity in blood platelets and muscle biopsies has been also reported [102, 103].”
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
Chomyn, A., Lai, S. T., Shakeley, R. M., Bresolin, N., Scarlato, G., & Attardi, G. M. (1994) · PubMed Central · Cited by 135
Zhou, Y. F., Shie, F., Piccardo, P., Montine, T. J., & Zhang, J. (2004) · Neuroscience · doi:10.1016/j.neuroscience.2004.06.048 · Cited by 135
Jin, J., Meredith, G. E., Chen, L., Zhou, Y. F., Xu, J., Shie, F., Lockhart, P. J., & Zhang, J. (2004) · Molecular Brain Research · doi:10.1016/j.molbrainres.2004.10.003 · Cited by 129
Oxidative stress in Parkinson’s disease
Nikam, S., Nikam, P., Ahaley, S. K., & Sontakke, A. V. (2009) · Indian Journal of Clinical Biochemistry · doi:10.1007/s12291-009-0017-y · Cited by 126
Gu, G., Reyes, P. F., Golden, G. T., Woltjer, R. L., Hulette, C., Montine, T. J., & Zhang, J. (2002) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/61.7.634 · Cited by 122
“Several groups of investigators have reported inhibition of mitochondrial respiratory chain function in PD patients (2–4), although there is controversy as to whether there is a specific inhibition of complex I alone or whether other complexes also are affected (5, 6).”
BackgroundEsteves, A. R., Domingues, A. F., Ferreira, I. L., Januário, C., Swerdlow, R. H., Oliveira, C. R., & Cardoso, S. M. (2008) · Mitochondrion · doi:10.1016/j.mito.2008.03.004 · Cited by 110
“Our data confirm prior studies showing complex I activity is reduced in PD subject platelets (Schapira and Marsden , 1994; Barroso et al., 1993; Parker et al., 1989; Yoshino et al., 1992; Benecke et al., 1993; Haas et al., 1995; Blandini et al., 1998).”
Norwitz, N. G., Hu, M. T., & Clarke, K. (2019) · Frontiers in Nutrition · doi:10.3389/fnut.2019.00063 · Cited by 110
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Swerdlow, R. H., Koppel, S., Weidling, I., Hayley, C., Ji, Y., & Wilkins, H. M. (2017) · Progress in Molecular Biology and Translational Science · doi:10.1016/bs.pmbts.2016.12.017 · Cited by 106
A Mitochondrial Etiology of Neurodegenerative Diseases: Evidence from Parkinson's Disease
Хуснутдинова, Э. К., Gilyazova, I. R., Ruiz‐Pesini, E., Derbeneva, O. A., Khusainova, R. I., Khidiyatova, I. M., Magzhanov, R. V., & Wallace, D. C. (2008) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1427.001 · Cited by 108
Grünewald, A., Gegg, M. E., Taanman, J., King, R. H. M., Kock, N., Klein, C., & Schapira, A. H. V. (2009) · Experimental Neurology · doi:10.1016/j.expneurol.2009.05.027 · Cited by 116
“Subsequently, complex I dysfunction has also been observed in platelets (Benecke et al., 1993; Krige et al., 1992; Parker et al., 1989) as well as in fibroblasts of patients (Hoepken et al.”
Platelets in Neurodegenerative Conditions—Friend or Foe?
Leiter, O., & Walker, T. L. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.00747 · Cited by 102
Ihara, Y., CHUDA, M., Kuroda, S., et al. (1999) · Journal of the Neurological Sciences · doi:10.1016/s0022-510x(99)00192-6 · Cited by 100
Hall, J. G. (1996) · American Journal of Medical Genetics · doi:10.1002/(sici)1096-8628(19960122)61:3 · Cited by 103
Mitochondrial Dysfunction in Idiopathic Parkinson Disease
Parker, W. D., & Swerdlow, R. H. (1998) · The American Journal of Human Genetics · doi:10.1086/301812 · Cited by 97
Chrysostome, V., Tison, F., Yekhlef, F., Sourgen, C., Baldi, I., & Dartigues, J. (2004) · Neuroepidemiology · doi:10.1159/000078506 · Cited by 92
A possible role of coenzyme Q10 in the etiology and treatment of Parkinson's disease
Shults, C. W., Haas, R., & Beal, M. F. (1999) · BioFactors · doi:10.1002/biof.5520090223 · Cited by 91
“was subsequently confirmed by other investigators [3,14,27].”
Current perspective of mitochondrial biology in Parkinson's disease
Kaidery, N. A., & Thomas, B. (2018) · Neurochemistry International · doi:10.1016/j.neuint.2018.03.001 · Cited by 95
Rango, M., Bonifati, C., & Bresolin, N. (2005) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/sj.jcbfm.9600192 · Cited by 91
“Reduction in complex I activity has been reported in PD tissues (Benecke et al, 1993; Haas et al, 1995; Krige et al, 1992; Mizuno et al, 1989; Schapira et al, 1989, 1998; Swerdlow et al, 1996).”
BackgroundGhosh, S. S., Swerdlow, R. H., Miller, S. W., Sheeman, B., Parker, W. D., & DAVIS, R. E. (1999) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1999.tb07825.x · Cited by 91
Complex I Function Is Defective in Complex IV-deficient Caenorhabditis elegans
Suthammarak, W., Yang, Y.-Y., Morgan, P. G., & Sedensky, M. M. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m805733200 · Cited by 86
The multifaceted role of platelets in mediating brain function
Burnouf, T., & Walker, T. L. (2022) · Blood · doi:10.1182/blood.2022015970 · Cited by 86
Protective Effects of Asiatic Acid on Rotenone- or H2O2-Induced Injury in SH-SY5Y Cells
Xiong, Y., Ding, H., Minfang, X., & Gao, J. (2008) · Neurochemical Research · doi:10.1007/s11064-008-9844-0 · Cited by 85
Recent developments in the molecular genetics of mitochondrial disorders
Graeber, M. B., & Müller, U. (1998) · Journal of the Neurological Sciences · doi:10.1016/s0022-510x(97)00295-5 · Cited by 79
Therapeutic role of coenzyme Q10 in Parkinson's disease
Shults, C. W. (2005) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2005.02.002 · Cited by 81
“…have also reported a reduction of complex I activity in platelets, muscle, and lymphocytes (Bindoff et al., 1991; Shoffner et al., 1991; Krige et al., 1992; Nakagawa-Hattori et al., 1992; Yoshino et al., 1992; Barroso et al., 1993; Benecke et al., 1993; Cardellach et al., 1993; Blin et al., 1994).”
BackgroundPinto, M., Nissanka, N., Peralta, S., Brambilla, R., Díaz, F., & Moraes, C. T. (2016) · Molecular Neurodegeneration · doi:10.1186/s13024-016-0090-7 · Cited by 78
“Some groups found impaired complex II, complex II + III, and complex IV activity in platelets [6], whereas others reported a selective complex I inhibition [3].”
Effect of coenzyme Q10 on the mitochondrial function of skin fibroblasts from Parkinson patients
Winkler‐Stuck, K., Wiedemann, F. R., Wallesch, C., & Kunz, W. S. (2004) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2004.02.003 · Cited by 77
Parkinson's Disease: From Molecular Pathways in Disease to Therapeutic Approaches
Thomas, B. (2009) · Antioxidants and Redox Signaling · doi:10.1089/ars.2009.2697 · Cited by 76
“The former seems to be true since complex I activity does not correlate with levodopa dosage, and is normal in other neurodegenerative diseases, such as multiple system atrophy, suggesting that it is not a nonspecific consequence of neurodegeneration (2, 18).”
BackgroundBeyond Haemostasis and Thrombosis: Platelets in Depression and Its Co-Morbidities
Izzi, B., Tirozzi, A., Cerletti, C., Donati, M. B., de Gaetano, G., Hoylaerts, M., Iacoviello, L., & Gialluisi, A. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21228817 · Cited by 79
Gerlach, M., Maetzler, W., Broich, K., Hampel, H. J., Rems, L., Reum, T., Riederer, P. F., Stöffler, A., Streffer, J. R., & Berg, D. (2011) · Journal of Neural Transmission · doi:10.1007/s00702-011-0682-x · Cited by 74
Neuroprotective effect of catalpol against MPP+-induced oxidative stress in mesencephalic neurons
Tian, Y., Jiang, B., An, L., & Bao, Y. (2007) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2007.04.039 · Cited by 72
“The role of mitochondrial dysfunction in the pathogenesis of Parkinson's disease is also supported by the fact that the dopaminergic toxin MPTP inhibits complex I (Benecke et al., 1993).”
BackgroundRole of Mitochondria in Parkinson Disease
Kösel, S., Hofhaus, G., Maaßen, A., Vieregge, P., & Graeber, M. B. (1999) · Biological Chemistry · doi:10.1515/bc.1999.106 · Cited by 71
“In some patients, a decrease of complex I activity was also observed in platelets (Krige et al., 1992; Benecke et al., 1993) and skeletal muscle (Bindoff et al., 1991).”
BackgroundAlternative oxidase rescues mitochondria-mediated dopaminergic cell loss in Drosophila
Humphrey, D. M., Parsons, R. B., Ludlow, Z. N., Riemensperger, T. D., Esposito, G., Verstreken, P., Jacobs, H. T., Birman, S., & Hirth, F. (2012) · Human Molecular Genetics · doi:10.1093/hmg/dds096 · Cited by 75
“Moreover, this also indicates that respiratory chain deficiencies other than complex I, such as complex IV deficiencies also seen in Parkinson’s disease (53), significantly contribute to age-related neurodegeneration.”
BackgroundSuccinate dehydrogenase: Prospect for neurodegenerative diseases
Farshbaf, M. J., & Kiani‐Esfahani, A. (2017) · Mitochondrion · doi:10.1016/j.mito.2017.12.002 · Cited by 71
Chronic reduction in complex I function alters calcium signaling in SH-SY5Y neuroblastoma cells
Sherer, T., Trimmer, P. A., Borland, K., Parks, J. K., Bennett, J. P., & Tuttle, J. B. (2001) · Brain Research · doi:10.1016/s0006-8993(00)03203-0 · Cited by 69
Platelet mitochondrial respiratory chain function in Parkinson's disease
Blake, C. I., Spitz, E., Leehey, M. A., Hoffer, B. J., & Boyson, S. J. (1997) · Movement Disorders · doi:10.1002/mds.870120103 · Cited by 68
Mitochondrial dysfunctions in Parkinson's disease
Gautier, C., Corti, O., & Brice, A. (2013) · Revue Neurologique · doi:10.1016/j.neurol.2013.06.003 · Cited by 73
Mitochondrial respiratory chain function in multiple system atrophy
Gu, M., Gash, M. T., Cooper, J. A. D., Wenning, G. K., Daniel, S. E., Quinn, N. P., MARSDEN, C. D., & Schapira, A. H. V. (1997) · Movement Disorders · doi:10.1002/mds.870120323 · Cited by 66
Mitochondrial therapies for Parkinson's disease
Thomas, B., & Beal, M. F. (2010) · Movement Disorders · doi:10.1002/mds.22781 · Cited by 62
“dopa dosage, and is normal in other neurodegenerative diseases, such as Multiple System Atrophy (MSA), suggesting that it is not a nonspeciıc consequence of neurodegeneration.(12,13) A number of studies provide genetic evidence that abnormalities in mtDNA (mitochondrial DNA) may contribute to PD pathogenesis.”
BackgroundDonatti, A., do Canto, A. M., Godoi, A. B., da Rosa, D. C., & Lopes‐Cendes, Í. (2020) · Metabolites · doi:10.3390/metabo10100389 · Cited by 69
Mitochondrial complex I deficiency stratifies idiopathic Parkinson’s disease
Flønes, I. H., Toker, L., Sandnes, D. A., Castelli, M., Mostafavi, S., Lura, N. G., Shadad, O., Fernández‐Vizarra, E., Painous, C., Pérez‐Soriano, A., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-47867-4 · Cited by 67
Bioenergetic and proteolytic defects in fibroblasts from patients with sporadic Parkinson's disease
Ambrosi, G., Ghezzi, C., Sepe, S., Milanese, C., Payán‐Gómez, C., Bombardieri, C. R., Armentero, M., Zangaglia, R., Pacchetti, C., Mastroberardino, P. G., et al. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2014.05.008 · Cited by 60
“Also, in previous studies performed on peripheral cells obtained frompatients, reducedmitochondrial complex I activity was identified as a critical feature to discriminate PD samples from controls, as well as patients with other neurodegenerative disorders [8,9,46,47].”
Schägger, H. (1996) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(96)64048-8 · Cited by 60
PINK1-Interacting Proteins: Proteomic Analysis of Overexpressed PINK1
Raković, A., Grünewald, A., Voges, L., Hofmann, S., Orolicki, S., Lohmann, K., & Klein, C. (2011) · Parkinson s Disease · doi:10.4061/2011/153979 · Cited by 58
“Complex IV deficiency in turn, has been implicated in PD [40, 41] opening the possibility for a role of HSP60 in the pathogenesis of the disease.”
BackgroundChoi, H. J., Lee, S. Y., Cho, Y., No, H., Kim, S. W., & Hwang, O. (2005) · Neurochemistry International · doi:10.1016/j.neuint.2005.10.011 · Cited by 58
“The role of mitochondrial dysfunction in the pathogenesis of PD is also supported by the fact that the dopaminergic toxin MPTP inhibits complex I (Benecke et al., 1993) and the complex I inhibitor rotenone can reproduce neuropathological features of PD (Schapira, 1994).”
BackgroundInfluentialMitochondrial DNA polymorphisms in pathologically proven Parkinson’s disease
Bandmann, O., Sweeney, M. G., Daniel, S. E., MARSDEN, C. D., & Wood, N. W. (1997) · Journal of Neurology · doi:10.1007/s004150050082 · Cited by 53
Mutations in Mitochondrial Complex III Uniquely Affect Complex I in Caenorhabditis elegans
Suthammarak, W., Morgan, P. G., & Sedensky, M. M. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.159608 · Cited by 54
Astrocytes Attenuate Mitochondrial Dysfunctions in Human Dopaminergic Neurons Derived from iPSC
Du, F., Yu, Q., Chen, A., Chen, D., & Yan, S. S. (2018) · Stem Cell Reports · doi:10.1016/j.stemcr.2017.12.021 · Cited by 54
“In addition, combined decreased complex I and IV activity was seen in the platelet mitochondria of PD (Benecke et al., 1993) and 1-methyl-4-phenyl 1,2,3,6-tetrahydropyridine (MPTP)- or 6-hydroxydopamine-induced animal models of PD (Desai et al.”
BackgroundOxidative stress in skin fibroblasts cultures from patients with Parkinson's disease
del Hoyo, P., García‐Redondo, A., Bustos, F., Molina, J. A., Sayed, Y., Alonso‐Navarro, H., Caballero, L., Arenas, J., Agúndez, J. A. G., & Jiménez‐Jiménez, F. J. (2010) · BMC Neurology · doi:10.1186/1471-2377-10-95 · Cited by 50
“There have been reported normal activities [6,18-20], or decreased activities of complex I [21-26], complex II+III [25] or complex IV [24].”
BackgroundReduced platelet glutamate uptake in Parkinson's disease
Ferrarese, C., Zoia, C., Pecora, N., Piolti, R., Frigo, M., Bianchi, G., Sala, G., Begni, B., Riva, R., & Frattola, L. (1999) · Journal of Neural Transmission · doi:10.1007/s007020050189 · Cited by 51
“However, defects in complex-1 mitochondrial enzymes, which make dopaminergic cells more sensitive to oxidative stress, have been found not only in substantia nigra of PD patients (Hattori et al., 1991), but also in peripheral tissues (Shoffner et al., 1991) and in blood platelets ( Benecke et al., 1993; Krige et al.,…”
BackgroundResultMitochondrial DNA–Related Mitochondrial Dysfunction in Neurodegenerative Diseases
Swerdlow, R. H. (2002) · Archives of Pathology & Laboratory Medicine · doi:10.5858/2002-126-0271-mdrmdi · Cited by 50
Subrahmanian, N., & LaVoie, M. J. (2021) · Brain Research · doi:10.1016/j.brainres.2021.147434 · Cited by 48
“Five studies from four different research groups considering samples from 98 PD patients observed a 16–51% decrease in isolated CI activity or combined with CII and CIV deficiency, with no significant correlation between CI deficiency and age at onset, duration of disease, or severity of disease (Benecke et al., 1993;…”
BackgroundResultInfluentialA Complex Genome-MicroRNA Interplay in Human Mitochondria
Shinde, S., & Bhadra, U. (2015) · BioMed Research International · doi:10.1155/2015/206382 · Cited by 49
In vivo vulnerability of dopamine neurons to inhibition of energy metabolism
Zeevalk, G. D., Manzino, L., Hoppe, J., & Sonsalla, P. K. (1997) · European Journal of Pharmacology · doi:10.1016/s0014-2999(96)00892-8 · Cited by 49
Emerging (and converging) pathways in Parkinson's disease: keeping mitochondrial wellness
Cieri, D., Brini, M., & Calí, T. (2016) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2016.08.153 · Cited by 50
Peripheral markers of oxidative stress in Parkinson’s disease. the role of L-DOPA
Martignoni, E., Blandini, F., Godi, L., Desideri, S., Pacchetti, C., Mancini, F., & Nappi, G. (1999) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(99)00075-1 · Cited by 47
Assessment of Platelet Respiration as Emerging Biomarker of Disease
Petruş, A., Lighezan, D. L., Dănilă, M. D., Duicu, O., Sturza, A., Muntean, D. M., & Ioniță, I. (2019) · Physiological Research · doi:10.33549/physiolres.934032 · Cited by 47
“Ageing Decreased stability of CI Decreased energy conservation Decreased CIV activity (D'Aurelio et al. 2001) Asthma Astmatic patients present increased oxygen utilization and efficients usage of substrates in platelets as previously shown in the airways (Weiling Xu 2015) Pulmonary hypertension - Increased mitochondri…”
BackgroundInfluentialMITOCHONDRIAL COMPLEX I, II/III, AND IV ACTIVITIES IN FAMILIAL AND SPORADIC PARKINSON'S DISEASE
Hanagasi, H. A., AYRIBAS, D., Baysal, K., & Emre, M. (2005) · International Journal of Neuroscience · doi:10.1080/00207450590523017 · Cited by 45
“…mitochondria, the severity of the complex I defect in PD varies from 16 to 71% in published studies (Parker et al., 1989; Yoshino et al., 1992; Benecke et al., 1993; Krige et al., 1993; Haas et al., 1995); some groups have reported normal complex I activity in platelets (Bravi et al., 1992;…”
BackgroundInfluentialGenetic aspects of Parkinson's disease
Bandmann, O., MARSDEN, C. D., & Wood, N. W. (1998) · Movement Disorders · doi:10.1002/mds.870130203 · Cited by 47
Quantitative study of mitochondrial complex I in platelets of parkinsonian patients
Blandini, F., Nappi, G., & Timothy Greenamyre, J. (1998) · Movement Disorders · doi:10.1002/mds.870130106 · Cited by 44
Early-onset Parkinson disease caused by a mutation in CHCHD2 and mitochondrial dysfunction
Lee, R. G., Sedghi, M., Salari, M., Shearwood, A.-M. J., Stentenbach, M., Kariminejad, A., Goullée, H., Rackham, O., Laing, N. G., Tajsharghi, H., et al. (2018) · Neurology Genetics · doi:10.1212/nxg.0000000000000276 · Cited by 46
“Although reduced complex IV activity has been previously reported in PD, there is much less evidence for impaired complex IV activity, contributing to PDdevelopment.(27) The reduction in complex IV formation is consistent with studies finding an interaction between CHCHD2 and the cytochrome c–binding protein MICS1.”
BackgroundMitochondrial dysfunction and possible treatments in Parkinson's disease—a review
Shults, C. W. (2004) · Mitochondrion · doi:10.1016/j.mito.2004.07.028 · Cited by 44
Kim, C. B. Y., Pier, L. P., & Spear, P. D. (1997) · The Anatomical Record · doi:10.1002/(sici)1097-0185(199701)247:1 · Cited by 42
Swerdlow, R. H., Parks, J. K., Cassarino, D. S., Binder, D. R., Bennett, J. P., Iorio, G. D., Golbe, L. I., & Parker, W. D. (2001) · Experimental Neurology · doi:10.1006/exnr.2001.7674 · Cited by 43
Novel mitochondrial DNA mutations in Parkinson's disease
Richter, G., Sonnenschein, A., Grünewald, T. G. P., Reichmann, H., & Janetzky, B. (2002) · Journal of Neural Transmission · doi:10.1007/s007020200060 · Cited by 42
“Furthermore decreased enzyme activities were reported in muscle, fibroblasts and platelets (Benecke et al., 1993; Haas et al., 1995; Krige et al., 1992; Wiedemann et al., 1999).”
Metadata
- Authors
- Benecke, R., Strumper, P., & Weiss, H.
- Affiliations
- Heinrich Heine University Düsseldorf (DE)
- Corresponding author
- Benecke, R.
- ORCID
- Benecke, R.
- Venue
- Brain
- Publisher
- Oxford University Press (OUP)
- Published
- 1993-12-01
- Volume
- 116
- Issue
- 6
- Pages
- 1451-1463
- ISSN
- 0006-8950 (ISSN-L)
- 1460-2156
- OpenAlex
- W2005045122
- Cited by
- 220
- References
- 0
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 5 · 2023: 6 · 2022: 6 · 2021: 1 · 2020: 7 · 2019: 5 · 2018: 9 · 2017: 6 · 2016: 4 · 2015: 6 · 2014: 4 · 2013: 5 · 2012: 6
- FWCI
- 4.83
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- Topics
- Health Sciences › Medicine › Clinical 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, atypical parkinsonism, multiple system atrophy, electron transfer complex, complex I, cytochrome bc1 complex, cytochrome c oxidase, platelet mitochondria, mitochondrial enzyme activity, disease duration
- MeSH terms
- Aged, Aged, 80 and over, Blood Platelets, Electron Transport Complex IV, Electron Transport, Humans, Middle Aged, Mitochondria, Parkinson Disease, Parkinson Disease, Secondary, Syndrome, Electron Transport Complex III, NAD(P)H Dehydrogenase (Quinone)
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