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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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Aging, energy, and oxidative stress in neurodegenerative diseases
Beal, M. F. (1995) · Annals of Neurology · doi:10.1002/ana.410380304 · Cited by 1,434
Effects of Coenzyme Q10 in Early Parkinson Disease: Evidence of Slowing of the Functional Decline
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
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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