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Mitochondrial dysfunction in Parkinson's disease
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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 [10]
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MITOCHONDRIAL COMPLEX I DEFICIENCY IN PARKINSON'S DISEASE
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“PD is also associated with mitochondrial dysfunction, including impaired mitochondrial dynamics and oxidative stress [282], and oxidative stress has been linked to alpha-synuclein accumulation in dopaminergic neurons, a hallmark of the disease [283].”
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“Just like mHtt is linked to HD, abnormal bamyloid (Ab) peptide processing is linked to AD, and mutations in a-synuclein, parkin, DJ-1, PINK1, and LRRK2 are linked to PD (Lin and Beal 2006; Schapira 2007; Gotz et al. 2009; Chan et al. 2009).”
BackgroundG2019S leucine-rich repeat kinase 2 causes uncoupling protein-mediated mitochondrial depolarization
Papkovskaia, T. D., Chau, K., Iñesta-Vaquera, F., Papkovsky, D. B., Healy, D. G., Nishio, K., Staddon, J. M., Duchen, M. R., Hardy, J., Schapira, A. H. V., et al. (2012) · Human Molecular Genetics · doi:10.1093/hmg/dds244 · Cited by 168
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“Decreased mitochondrial complex-I activity was observed in platelets, SN and skeletal muscle of PD patients (Bindoff et al. 1989; Schapira et al. 1990; Haas et al. 1995; Schapira 2007).”
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“…humans and animal models (Betarbet et al. 2002; Corti et al. 2005); a high proportion of sporadic PD patients exhibit systemic mitochondrial defects (Schapira 2007); mitochondrial DNA deletions are present at high abundance in dopamine neurons from aged individuals, and are even more prevalent in…”
BackgroundAlpha-Synuclein as a Biomarker of Parkinson’s Disease: Good, but Not Good Enough
Ganguly, U., Singh, S., Pal, S., Prasad, S., Agrawal, B. K., Saini, R. V., & Chakrabarti, S. (2021) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2021.702639 · Cited by 139
“Mitochondrial complex I inhibition in substantia nigra in postmortem PD brain was an early finding which was later reported in platelets and skeletal muscles of PD patients (Schapira, 2007).”
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“In addition, preclinical and clinical findings have revealed that brain and cerebrospinal fluid samples from PD patients contain significantly higher levels of oxidized coenzyme Q10 and the nuclear DNA oxidation biomarker 8-OHdG, establishing the existence of oxidative damage to DNA and mitochondria in PD patients [59…”
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“This phenomenon leads to oxidative stress and thereby selective neurodegeneration (Li, Niu, et al., 2019; Schapira, 2007).”
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Self-citationSelective neuronal vulnerability in Parkinson's disease
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“…activity has been observed in the substantia nigra (SN) of patients affected by PD (Ambani et al. 1975; Kish et al. 1985; Marttila et al. 1988; Saggu et al. 1989; Sian et al. 1994; Fukae et al. 2007) and mitochondrial dysfunctions are known to be involved in PD pathogenesis (Schapira 2007).”
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“…dysfunction have been found in postmortem Parkinson’s disease brains (Bindoff et al. 1989; Schapira et al. 1990; Parker and Swerdlow 1998; Beal 2003; Schapira 2007; Chu et al. 2009; Swerdlow 2009; Ryan et al. 2015), as well as dopaminergic neurons derived from patients with idiopathic and familial…”
BackgroundChanges in endoplasmic reticulum stress proteins and aldolase A in cells exposed to dopamine
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“…DAQ has been shown to inhibit the activity of mitochondrial protein complexes (including complex I), to uncouple mitochondrial respiration, and to open the permeability transition pore (Ben-Shachar et al. 1995; Berman and Hastings 1999; Li and Dryhurst 2001; Khan et al. 2005; Schapira 2007).”
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“…not clearly understood, a variety of molecular mechanisms have been proposed to explain the dopaminergic cell death phenomenon, including mitochondrial dysfunction, oxidative stress, and activation of microglia in the substantia nigra (Abou-Sleiman et al., 2006; Block et al., 2007; Schapira, 2007).”
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“…2005; Danielson et al., 2011; Dawson and Dawson, 2003; Fato et al., 2008b; Henchcliffe and Beal, 2008; Perier et al., 2007; Schapira et al., 1989; Schapira, 2007; Sterky et al., 2012; Winklhofer and Haass, 2010), increased excitotoxicity, altered calcium homeostasis (Lang, 2007; Maetzler et al.,…”
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“α-synuclein aggregation and mitochondrial dysfunction exacerbate each other and are both important elements in PD pathogenesis [89,90,92].”
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Mitochondrial dysfunction in Parkinson’s disease
Бунеева, О. А., & Medvedev, A. E. (2011) · Biochemistry (Moscow) Supplement Series B Biomedical Chemistry · doi:10.1134/s1990750811040032 · Cited by 30
Ding, Y., Xin, C., Zhang, C., Lim, K., Zhang, H., Fu, Z., Li, L., & Huang, W. (2018) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2018.00246 · Cited by 28
“Mutation of genes involved in mitochondrial homeostasis was known to induce familial PD (Schapira, 2007).”
BackgroundFrom Brain to Muscle: The Role of Muscle Tissue in Neurodegenerative Disorders
Duranti, E., & Villa, C. (2024) · Biology · doi:10.3390/biology13090719 · Cited by 31
“Similarly, in PD, α -syn aggregates form Lewy bodies in the brain and have been detected in muscle tissue, compromising cellular homeostasis [214].”
BackgroundLeaver, K. R., Allbutt, H. N., Creber, N. J., Kassiou, M., & Henderson, J. M. (2009) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2009.08.013 · Cited by 27
Arduíno, D. M., Esteves, A. R., Swerdlow, R. H., & Cardoso, S. M. (2015) · Methods in molecular biology · doi:10.1007/978-1-4939-2288-8_31 · Cited by 27
Exposure to Phosphoglycerate Kinase 1 Activators and Incidence of Parkinson's Disease
Gros, P., Wang, X., Guan, J., Lang, A. E., Austin, P. C., Welk, B. K., Visanji, N. P., & Marras, C. (2021) · Movement Disorders · doi:10.1002/mds.28712 · Cited by 26
Involvement of antioxidant enzymes in Parkinson’s disease
Tahavvori, A., Gargari, M. K., Yazdani, Y., Mamalo, A. S., Beilankouhi, E. A. V., & Valilo, M. (2023) · Pathology - Research and Practice · doi:10.1016/j.prp.2023.154757 · Cited by 28
Pathania, A., Garg, P., & Sandhir, R. (2021) · Metabolic Brain Disease · doi:10.1007/s11011-021-00840-2 · Cited by 25
“Furthermore, reduced citrate synthase activity has been supported by Schapira (2007) in the SNregion of patients with multiple system atrophy (Parkinsonianlike disorder).”
BackgroundProtective Effects of the Caffeine Against Neurodegenerative Diseases
Tellone, E., Galtieri, A., Russo, A., & Ficarra, S. (2017) · Current Medicinal Chemistry · doi:10.2174/0929867324666171009104040 · Cited by 25
Juárez‐Flores, D. L., Ezquerra, M., González‐Casacuberta, I., Ormazábal, A., Morén, C., TOLOSA, E. S., Fucho, R., Guitart‐Mampel, M., Casado, M., Valldeoriola, F., et al. (2020) · Antioxidants · doi:10.3390/antiox9111063 · Cited by 24
“Specifically, mitochondrial respiratory chain (MRC) dysfunction, oxidative stress, altered mitochondrial dynamics, and morphology have been reported in iPD [21].”
BackgroundSandeep, X. X. X. X., Ahmad, M. H., Rani, L., & Mondal, A. C. (2022) · Molecular Neurobiology · doi:10.1007/s12035-022-02867-7 · Cited by 24
Mursaleen, L., Chan, S. H. Y., Noble, B., Somavarapu, S., & Zariwala, M. G. (2023) · Antioxidants · doi:10.3390/antiox12010130 · Cited by 23
Exercise and mitochondrial remodeling to prevent age-related neurodegeneration
O’Reilly, C. L., Miller, B. F., & Lewis, T. L. (2022) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00611.2022 · Cited by 25
Serrano‐García, N., Fernández‐Valverde, F., Luis‐García, E. R., Granados-Rojas, L., Juárez-Zepeda, T. E., Orozco-Suárez, S. A., Pedraza‐Chaverrí, J., Orozco‐Ibarra, M., & Jiménez‐Anguiano, A. (2018) · Neurochemistry International · doi:10.1016/j.neuint.2018.10.015 · Cited by 23
“Indeed, mitochondrial complex I activity decreases between 20 and 30% in the SNpc and frontal cortex in patients with idiopathic PD (Schapira, 2007; Navarro et al., 2009; Chaturvedi and Beal, 2013).”
Cross-talk between α-synuclein and the microtubule cytoskeleton in neurodegeneration
Mazzetti, S., Calogero, A. M., Pezzoli, G., & Cappelletti, G. (2022) · Experimental Neurology · doi:10.1016/j.expneurol.2022.114251 · Cited by 22
Metadata
- Authors
- Schapira, A. H. V.
- Affiliations
- The Royal Free Hospital (GB)
- Corresponding author
- Schapira, A H V
- ORCID
- Schapira, A H V
- Venue
- Cell Death & Differentiation
- Published
- 2007-04-27
- Volume
- 14
- Issue
- 7
- Pages
- 1261-1266
- ISSN
- 1350-9047 (ISSN-L)
- 1476-5403
- OpenAlex
- W1990162995
- Cited by
- 175
- References
- 95
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 7 · 2023: 7 · 2022: 13 · 2021: 12 · 2020: 10 · 2019: 8 · 2018: 9 · 2017: 9 · 2016: 3 · 2015: 13 · 2014: 7 · 2013: 14 · 2012: 6
- FWCI
- 1.46
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Cell Death and Differentiation (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Receptors and Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Keywords
- Parkinson's disease, mitochondrial dysfunction, dopaminergic neuron loss, substantia nigra, PINK1, DJ-1, OMI, PARK genes, familial Parkinson's disease, sporadic Parkinson's disease, oxidative damage, neuroinflammation, proteasomal dysfunction, mitochondrial respiratory chain, genetic mutations
- MeSH terms
- Protein Deglycase DJ-1, PTEN-Induced Putative Kinase, Animals, DNA, Mitochondrial, Humans, Mitochondria, Mutation, Parkinson Disease, Protein Kinases, Oncogene Proteins, Mitochondrial Diseases, Electron Transport Complex I, Ubiquitin-Protein Ligases, Intracellular Signaling Peptides and Proteins
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