The DOI matches its Crossref record; 33 of the 33 references it cites were found in a registry or an index; none of the 19 sources its claims cite is checked for support yet.
Progressive parkinsonism in mice with respiratory-chain-deficient dopamine neurons
Open accessAbstract
Mitochondrial dysfunction is implicated in the pathophysiology of Parkinson′s disease (PD), a common age-associated neurodegenerative disease characterized by intraneuronal inclusions (Lewy bodies) and progressive degeneration of the nigrostriatal dopamine (DA) system. It has recently been demonstrated that midbrain DA neurons of PD patients and elderly humans contain high levels of somatic mtDNA mutations, which may impair respiratory chain function. However, clinical studies have not established whether the respiratory chain deficiency is a primary abnormality leading to inclusion formation and DA neuron death, or whether generalized metabolic abnormalities within the degenerating DA neurons cause secondary damage to mitochondria. We have used a reverse genetic approach to investigate this question and created conditional knockout mice (termed MitoPark mice), with disruption of the gene for mitochondrial transcription factor A ( Tfam ) in DA neurons. The knockout mice have reduced mtDNA expression and respiratory chain deficiency in midbrain DA neurons, which, in turn, leads to a parkinsonism phenotype with adult onset of slowly progressive impairment of motor function accompanied by formation of intraneuronal inclusions and dopamine nerve cell death. Confocal and electron microscopy show that the inclusions contain both mitochondrial protein and membrane components. These experiments demonstrate that respiratory chain dysfunction in DA neurons may be of pathophysiological importance in PD.
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TL;DR
MitoPark mice with conditional Tfam disruption in midbrain dopamine neurons develop respiratory chain deficiency, adult-onset progressive parkinsonism, intraneuronal inclusions, and dopamine neuron death. The findings provide genetic evidence that respiratory chain dysfunction in dopamine neurons may be pathophysiologically important in Parkinson’s disease.
Key findings
- MitoPark mice had reduced mtDNA expression in midbrain DA neurons at 6 weeks and marked reduction of COX enzyme activity at 20 weeks.
- Motor impairment began at ≈14–15 weeks, progressed to tremor, twitching, and apparent limb rigidity at ≈20 weeks, and mice were killed at ≈45 weeks; L-DOPA improved motor performance, with older mice showing abrupt termination resembling “wearing off.”
- DA innervation loss first appeared in dorsolateral striatum at 12 weeks; TH+ midbrain neuron loss was earlier and more marked in SN than VTA, and 20-week-old MitoPark mice had DA loss plus increased HVA/DA and DOPAC/DA ratios.
- Most midbrain DA neurons contained small cytoplasmic inclusions at 6 weeks before DA cell loss; inclusions contained mitochondrial protein and membrane components by confocal and electron microscopy, but did not contain α-synuclein and persisted in α-synuclein knockout MitoPark mice.
Methods
- Reverse genetic conditional knockout: DAT-cre mice were crossed with TfamloxP/TfamloxP mice to disrupt Tfam in midbrain DA neurons; cre expression was validated by in situ hybridization and reporter mice.
- Behavioral testing used automated activity cages for locomotion and rearing, with L-DOPA plus benserazide or PBS injections; histology, immunohistochemistry, in situ hybridization, electron microscopy, confocal microscopy, and HPLC catecholamine measurements were used.
- Sample sizes included 7 MitoPark/control pairs for in situ hybridization and enzyme histochemistry, 20 pairs for immunohistochemistry, 18 mice (9 littermate pairs) for TH cell counts, and 9 animals for aggregate counts and size measurements.
Limitations
- The paper states that the mechanism whereby respiratory chain deficiency leads to inclusion formation needs to be elucidated, that there was no evidence of α-synuclein in the inclusions, and that there is no absolute link between respiratory chain dysfunction and oxidative stress.
- The text makes evident that this is a mouse model rather than human PD, that the inclusions differ from human Lewy bodies in α-synuclein content, and that the h116–131 antibody reacted with an unknown inclusion component.
- The paper does not include a formal limitations section; additional limitations evident from the text include reliance on a single conditional knockout model and unresolved specificity of one α-synuclein antibody.
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25 Own result · 11 Own interpretation · 8 Not checked yet · 1 Own method · 1 No basis given
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In the paper
“In situ hybridizations detected much reduced expression of the mtDNA-encoded COX subunit I mRNA in DA neurons of substantia nigra (SN) and the ventral tegmental area (VTA) in MitoPark mice at the age of 6 weeks (Fig. 1E).”
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In the paper
“accompanied by formation of intraneuronal inclusions and dopamine nerve cell death.”
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In the paper
“We also found a marked reduction of COX enzyme activity by histochemical analyses of midbrain DA neurons of 20-week-old MitoPark mice (Fig. 1D).”
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In the paper
“There was no increased embryonic or neonatal lethality in MitoPark mice.”
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“However, five additional antibodies (see Methods) directed against α-synuclein were not immunoreactive with the inclusions although they gave rise to expected α-synuclein-like immunoreactivity in nonaffected neurons.”
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In the paper
“accompanied by formation of intraneuronal inclusions and dopamine nerve cell death.”
- Also stated in: § Results · plain
“a majority of them contained small cytoplasmic aggregates (Fig. 4A–D).”
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In the paper
“We found many examples where a mitochondrial marker protein, the nucleus-encoded α-subunit of mitochondrial ATP synthase, partially overlapped with, was juxtaposed to, or even surrounded the inclusions (Fig. 4 E and F).”
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In the paper
“Decreased locomotion and reduced exploratory behavior first became apparent at age ≈14–15 weeks.”
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“The absence of a functional α-synuclein gene had no obvious impact on the phenotype in MitoPark mice (data not shown).”
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In the paper
“Confocal and electron microscopy show that the inclusions contain both mitochondrial protein and membrane components.”
- Also stated in: § Results · hedged
“We found many examples where a mitochondrial marker protein, the nucleus-encoded α-subunit of mitochondrial ATP synthase, partially overlapped with, was juxtaposed to, or even surrounded the inclusions (Fig. 4 E and F).”
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- It may state two separate claims as one. 13
- Probably not a substantial claim. 6
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In the paper
“Unexpectedly, the inclusions also remained, and were immunoreactive with the h116–131 antibody in the MitoPark mice lacking a functional α-synuclein gene (data not shown).”
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In the paper
“Quantification of numbers of tyrosine hydroxylase (TH)-expressing midbrain neurons revealed a slow progressive cell loss, which was more marked and had an earlier onset in SN, which predominantly innervates dorsal striatum, in comparison with VTA, which predominantly innervates ventral striatum and cortical areas (Fig. 3 E–I).”
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In the paper
“Loss of DA innervation was first observed in dorsolateral striatum at age 12 weeks and this loss progressed to involve most of the dorsal and ventral striatum as the MitoPark mice became older (Fig. 3A–D).”
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“The inclusions were present in most midbrain DA neurons (Fig. 4C) and their mean size increased as neurodegeneration progressed (Fig. 4D).”
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“Some of these bodies had an amorphous content and a diffuse lining, whereas others displayed tubular formations and were surrounded by distinct double layer membranes (Fig. 5 B and C).”
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In the paper
“In 6-week-old MitoPark mice, there was no observable DA cell loss (Fig. 3F) despite the presence of severely reduced mtDNA expression (Fig. 1E) in midbrain DA neurons.”
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Thus α-synuclein was neither needed for the PD phenotype nor the development of DA neuron inclusions in our mice.”
plain- Asserted: passes — The authors put it forward as true.
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- Rests on an assumption: α-synuclein is commonly found in Lewy bodies in human PD.
In the paper
“Available data show that Lewy bodies can have a variety of morphological shapes (25), and it has been suggested that their morphology evolves with time (25).”
What the sources say
- Not checked yetcites [25] Shults CW. Proc Natl Acad Sci USA. 2006;103:1661–1668. doi: 10.1073/pnas.0509567103. [DOI] [PMC free article] [PubMed] [Google Scholar]
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“The morphology of Lewy bodies has mainly been studied in brain tissue obtained from end-stage PD patients, and it is therefore not well established how these aggregates appear at early disease stages.”
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In the paper
“We used in situ hybridizations (Fig. 1B) and mating to reporter mice (23), which activate the expression of β-galactosidase in cre-expressing cells (Fig. 1C), to establish that DAT-cre mice express cre mRNA and enzymatically active cre-recombinase protein in DA neurons of the midbrain.”
What the sources say
- Not checked yetcites [23] Soriano P. Nat Genet. 1999;21:70–71. doi: 10.1038/5007. [DOI] [PubMed] [Google Scholar]
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“This differential degeneration is also characteristic of PD in man.”
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“It has recently been demonstrated that midbrain DA neurons of PD patients and elderly humans contain high levels of somatic mtDNA mutations, which may impair respiratory chain function.”
- Also stated in: § Abstract · boosted
“Analysis of mtDNA mutation levels in DA neurons with normal COX activity has demonstrated very high levels of mtDNA with deletions in both PD patients and aged controls and there was a linear increase of the mutation load with increasing age (7).”
What the sources say
- Not checked yetcites [7] Bender A, Krishnan KJ, Morris CM, Taylor GA, Reeve AK, Perry RH, Jaros E, Hersheson JS, Betts J, Klopstock T, et al. Nat Genet. 2006;38:515–517. doi: 10.1038/ng1769. [DOI] [PubMed] [Google Scholar] source
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In the paper
“We demonstrate that respiratory chain deficiency in DA neurons in mice leads to characteristic manifestations of parkinsonism, including slowly progressive neuronal degeneration, typical behavioral disturbances, and the formation of intraneuronal inclusions.”
boosteddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“In vitro studies have shown that α-synuclein can interact directly with lipids found in membranes (26, 27) and with proteins of the mitochondrial respiratory chain (28, 29).”
What the sources say
- Not checked yetcites [26] Cole NB, Murphy DD, Grider T, Rueter S, Brasaemle D, Nussbaum RL. J Biol Chem. 2002;277:6344–6352. doi: 10.1074/jbc.M108414200. [DOI] [PubMed] [Google Scholar]
- Not checked yetcites [27] Ellis CE, Murphy EJ, Mitchell DC, Golovko MY, Scaglia F, Barcelo-Coblijn GC, Nussbaum RL. Mol Cell Biol. 2005;25:10190–10201. doi: 10.1128/MCB.25.22.10190-10201.2005. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Not checked yetcites [28] Hashimoto M, Takeda A, Hsu LJ, Takenouchi T, Masliah E. J Biol Chem. 1999;274:28849–28852. doi: 10.1074/jbc.274.41.28849. [DOI] [PubMed] [Google Scholar]
- Not checked yetcites [29] Elkon H, Don J, Melamed E, Ziv I, Shirvan A, Offen D. J Mol Neurosci. 2002;18:229–238. doi: 10.1385/JMN:18:3:229. [DOI] [PubMed] [Google Scholar]
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What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“TH-immunoreactive DA nerve cell body profiles were counted on coded slides at representative levels of SN and VTA, respectively, using two to five sections per animal and a total of 18 mice (nine littermate pairs, each consisting of one MitoPark and one control).”
plainn = 18- Asserted: passes — The authors put it forward as true.
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In the paper
“The mitochondrial network has an elaborate system for protein degradation involving membrane bound AAA-proteases and LON protease in the matrix (31).”
What the sources say
- Not checked yetcites [31] Rugarli EI, Langer T. Trends Mol Med. 2006;12:262–269. doi: 10.1016/j.molmed.2006.04.002. [DOI] [PubMed] [Google Scholar]
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim.
The paper relies on this without support.
Clinical studies have not established whether respiratory chain deficiency is a primary abnormality leading to inclusion formation and DA neuron death, or whether generalized metabolic abnormalities within degenerating DA neurons cause secondary damage to mitochondria.
“However, clinical studies have not established whether the respiratory chain deficiency is a primary abnormality leading to inclusion formation and DA neuron death, or whether generalized metabolic abnormalities within the degenerating DA neurons cause secondary damage to mitochondria.”
The paper relies on this without support.
α-synuclein is commonly found in Lewy bodies in human PD.
“However, we did not find evidence of α-synuclein in these inclusions, although α-synuclein is commonly found in Lewy bodies in human PD.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“For all the targeted cell types, TFAM depletion leads to mtDNA depletion (not reported for midbrain DA neurons), mitochondrial transcript depletion (not reported for midbrain DA neurons) and respiratory chain deficiency, suggesting that TFAM is essential for mtDNA maintenance in vivo”
From Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases (2017) · cites this paper as Ekstrand et al., 2007
In the citing paper
“TFAM deletion in mouse pyramidal neurons causes mitochondrial late-onset neurodegeneration (MILON) (Sorensen et al., 2001) whereas deletion in mouse midbrain DA neurons leads to PD (Ekstrand et al., 2007).”
From Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases (2017) · cites this paper as Ekstrand et al., 2007
In the citing paper
“Alternative and more successful approaches to developing mouse models of mitochondrial disease involve manipulating the nuclear genes that regulate mtDNA maintenance and replication, such as TFAM [176][177][178][179][180][181][182], POLG ('Mutator' model) [183], and PEO1 (Twinkle; 'Deletor' model) [184].”
From Mitochondrial DNA mutations and human disease (2010) · cites this paper as [177]
Citations
Cites
Dauer, W., & Przedborski, S. (2003) · Neuron · doi:10.1016/s0896-6273(03)00568-3 · Cited by 5,469
Generalized lacZ expression with the ROSA26 Cre reporter strain
Soriano, P. (1999) · Nature Genetics · doi:10.1038/5007 · Cited by 5,237
Premature ageing in mice expressing defective mitochondrial DNA polymerase
Trifunovic, A., Wredenberg, A., Falkenberg, M., Spelbrink, J. N., Rovio, A. T., Bruder, C. E., Bohlooly-Y, M., Gidlöf, S., Oldfors, A., Wibom, R., et al. (2004) · Nature · doi:10.1038/nature02517 · Cited by 2,734
Self-citationDrosophila pink1 is required for mitochondrial function and interacts genetically with parkin
Clark, I. E., Dodson, M. W., Jiang, C., Cao, J. H., Huh, J. R., Seol, J. H., Yoo, S. J., Hay, B. A., & Guo, M. (2006) · Nature · doi:10.1038/nature04779 · Cited by 1,788
Mitochondrial dysfunction in Drosophila PINK1 mutants is complemented by parkin
Park, J., Lee, S. B., Lee, S., Kim, Y., Song, S., Kim, S., Bae, E., Kim, J., Shong, M., Kim, J.-M., et al. (2006) · Nature · doi:10.1038/nature04788 · Cited by 1,705
Mitochondrial transcription factor A is necessary for mtDNA maintance and embryogenesis in mice
Larsson, N.-G., Wang, J., Wilhelmsson, H., Oldfors, A., Rustin, P., Lewandoski, M., Barsh, G. S., & Clayton, D. A. (1998) · Nature Genetics · doi:10.1038/ng0398-231 · Cited by 1,594
Self-citationBender, A., Krishnan, K. J., Morris, C. M., Taylor, G. A., Reeve, A. K., Perry, R. H., Jaros, E., Hersheson, J. S., Betts, J., Klopstock, T., et al. (2006) · Nature Genetics · doi:10.1038/ng1769 · Cited by 1,570
Mitochondrial transcription factor A regulates mtDNA copy number in mammals
Ekstrand, M. I. (2004) · Human Molecular Genetics · doi:10.1093/hmg/ddh109 · Cited by 919
Self-citationVolkow, N. D., Wang, G.-J., Fowler, J. S., Gatley, S. J., Logan, J., Ding, Y.-S., Hitzemann, R., & Pappas, N. (1998) · American Journal of Psychiatry · doi:10.1176/ajp.155.10.1325 · Cited by 885
Cabin, D. E., Shimazu, K., Murphy, D., Cole, N. B., Gottschalk, W., McIlwain, K. L., Orrison, B., Chen, A., Ellis, C. E., Paylor, R., et al. (2002) · The Journal of Neuroscience · doi:10.1523/jneurosci.22-20-08797.2002 · Cited by 865
Research works printed but not linked: 1
- H Andersson, J Luthman, E Lindqvist, L Olson Neurotoxicology 16, 201–210 (1995).
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Fauss, D., Motter, R. N., Dofiles, L., Rodrigues, M. A. V., You, M., Diep, L., Yang, Y., Seto, P., Tanaka, K., Baker, J., et al. (2013) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2013.03.012 · Cited by 14
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Tyynismaa, H., & Suomalainen, A. (2010) · Methods · doi:10.1016/j.ymeth.2010.03.009 · Cited by 14
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“These results are supported by the observation that the homozygous aSyn knockout mice do not show obvious changes in the intensity of skin pigmentation [74,75].”
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Therapeutic potential of ATP-sensitive potassium channels in Parkinson’s disease
Zhao, S., Wang, M., & Ma, Z. (2021) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2021.01.003 · Cited by 16
Padhi, P., Abdalla, A., Schneider, B., Backes, N., Otto, A. A., Scheibe, I., Thomas, J. P., Khadse, G., Samidurai, M., Jochmans, A. K., et al. (2025) · Cell Host & Microbe · doi:10.1016/j.chom.2025.10.005 · Cited by 14
Xue, J., Zhang, J., Zhang, J., Liu, J., Wang, F., Liu, C., & Liu, C. (2023) · Mitochondrion · doi:10.1016/j.mito.2023.09.002 · Cited by 11
Cardanho‐Ramos, C., Simões, R. A., Wang, Y., Faria‐Pereira, A., Bomba-Warczak, E. K., Craessaerts, K., Spinazzi, M., Savas, J. N., & Morais, V. A. (2024) · iScience · doi:10.1016/j.isci.2024.109136 · Cited by 11
Paß, T., Ricke, K. M., Hofmann, P., Chowdhury, R., Nie, Y., Chinnery, P. F., Endepols, H., Neumaier, B., Carvalho, A. F., Rigoux, L., et al. (2024) · Brain · doi:10.1093/brain/awae089 · Cited by 14
Radlicka-Borysewska, A., Jabłońska, J., Lenarczyk, M., Szumiec, Ł., Harda, Z., Bagińska, M., Barut, J., Pera, J., Kreiner, G., Wojcik, D. K., et al. (2024) · Frontiers in Neuroscience · doi:10.3389/fnins.2024.1375265 · Cited by 12
“0297 in mutants, and an interaction effect on the preference over time (F(2, 38) = 3.”
BackgroundInfluentialEnergizing Genetics and Epi-genetics: Role in the Regulation of Mitochondrial Function
Audano, M., Ferrari, A., Fiorino, E., Künzl, M., Caruso, D., Mitro, N., Crestani, M., & Fabiani, E. D. (2015) · Current Genomics · doi:10.2174/138920291506150106151119 · Cited by 11
A Mitochondrial Perspective on Noncommunicable Diseases
Zheng, Y., Zhang, J., Zhu, X., Wei, Y., Zhao, W., Si, S., & Li, Y. (2023) · Biomedicines · doi:10.3390/biomedicines11030647 · Cited by 11
“Dysregulation of PGC-1α signaling during heart failure occurs at the transcriptional and post-transcriptional levels, contributing to the progression of cardiac dysfunction through multiple mechanisms [33].”
BackgroundMetabotropic glutamate receptors in Parkinson's disease
Kwan, C., Kang, W., Kim, E., et al. (2022) · International review of neurobiology · doi:10.1016/bs.irn.2022.10.001 · Cited by 10
Aging, Parkinson’s Disease, and Models: What Are the Challenges?
Bellantuono, I., Mortiboys, H., Rocha, E. M., Chamoli, M., Chinta, S. J., Andersen, J. K., Wallis, R., Bézard, E., Goldberg, M., Greenamyre, T., et al. (2023) · doi:10.59368/agingbio.20230010 · Cited by 13
“Mutations in the GBA1 gene, which encodes the lysosomal hydrolase glucocerebrosidase, are associated with sPD. Mutations in GBA1 and LRRK2 are considered as the highest genetic risk factors for developing sPD.”
BackgroundClement, A., Mitchelmore, C., Andersson, D. R., & Asuni, A. A. (2017) · Neuroscience · doi:10.1016/j.neuroscience.2017.04.030 · Cited by 10
Bimpisidis, Z., König, N., & Wallén‐Mackenzie, Å. (2020) · Journal of Visualized Experiments · doi:10.3791/60867 · Cited by 16
Wang, Y., Bouabid, S., Darvas, M., et al. (2020) · Experimental Neurology · doi:10.1016/j.expneurol.2020.113427 · Cited by 10
Fifel, K., Yanagisawa, M., & Deboer, T. (2022) · Advanced Science · doi:10.1002/advs.202203170 · Cited by 10
Kreiner, G. (2018) · Pharmacological Reports · doi:10.1016/j.pharep.2018.09.006 · Cited by 9
In vivo modeling of prodromal stage of Parkinson’s disease
Cerri, S., & Blandini, F. (2020) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2020.108801 · Cited by 9
Mitochondrial DNA Mutations and Ageing
Whitehall, J. C., Smith, A. L. M., & Greaves, L. C. (2023) · Sub-cellular biochemistry/Subcellular biochemistry · doi:10.1007/978-3-031-21410-3_4 · Cited by 9
Kuo, T., Chen, Y.-H., Wang, V., Huang, E. Y., Ma, K., Greig, N. H., Jung, Y. J., Choi, H.-I., Olson, L., Hoffer, B. J., et al. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24054687 · Cited by 9
“The internal structure of the mitochondria (cristae) is progressively lost as well [23].”
BackgroundMethodSelf-citationInsulin and Insulin-Sensitizing Drugs in Neurodegeneration: Mitochondria as Therapeutic Targets
Cardoso, S., Santos, R. X., Correia, S. C., Carvalho, C., Zhu, X., Lee, H., Casadesús, G., Smith, M. A., Perry, G. L., & Moreira, P. I. (2009) · Pharmaceuticals · doi:10.3390/ph2030250 · Cited by 10
“dopaminergic neurons and a progressive PD phenotype [128].”
BackgroundDo mitochondrial DNA mutations have a role in neurodegenerative disease?
Krishnan, K. J., Reeve, A. K., & Turnbull, D. M. (2007) · Biochemical Society Transactions · doi:10.1042/bst0351232 · Cited by 9
Mishra, R., & Upadhyay, A. (2025) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-025-05668-y · Cited by 11
Tseng, K.-Y., Kuo, T., Wang, V., Huang, E. Y., Ma, K., Olson, L., Hoffer, B. J., & Chen, Y.-H. (2022) · Journal of Parkinson s Disease · doi:10.3233/jpd-223195 · Cited by 8
Self-citationHuang, M., Jin, H., Anantharam, V., Kanthasamy, A., & Kanthasamy, A. G. (2024) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2024.1422362 · Cited by 9
Sterky, F. H., Pernold, K., Harvey, B. K., Lindqvist, E., Hoffer, B. J., & Olson, L. (2012) · Cell Transplantation · doi:10.3727/096368912x657693 · Cited by 8
“found that MitoPark mice at this age (~15 weeks) had a ~40% reduction in cell numbers, consistent with previous reports (10).”
BackgroundResultInfluentialSelf-citationLang, M., Grünewald, A., Pramstaller, P. P., Hicks, A. A., & Pichler, I. (2022) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-022-04304-3 · Cited by 8
“The MitoPark mice, with disruption of the gene for mitochondrial transcription factor A (TFAM) in dopaminergic neurons, are characterized by a marked depletion of mtDNA, impairment of oxidative phosphorylation, dopaminergic neuron degeneration and motor deficits that mimic human parkinsonism [170].”
BackgroundCharli, A., Luo, J., Palanisamy, B., Malovic, E., Riaz, Z., Miller, C., Chang, Y.-T., Samidurai, M., Zenitsky, G. D., Jin, H., et al. (2025) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2025.1549265 · Cited by 7
“…and exhibit pathological features including mitochondrial dysfunction (Ekstrand et al., 2007) as they relate to human PD. MitoPark mice show significantly decreased locomotion and rearing behavior by age 16 wk when progressive nigrostriatal DAergic degeneration begins (Ekstrand et al., 2007).”
InfluentialCNS Mitochondria‐Derived Vesicle in Blood: Potential Biomarkers for Brain Mitochondria Dysfunction
Liu, Q., Chen, W., Wu, Y., Guo, Z., Chen, J., Tian, C., Wang, P., Zeng, S., Xu, B., Duan, J., et al. (2025) · Annals of Clinical and Translational Neurology · doi:10.1002/acn3.70060 · Cited by 7
“The reduced expression of mtDNA-encoded cytochrome c subunit I and decreased cytochrome c activity further support the role of mitochondrial dysfunction in PD [23].”
Thomas, C., Shilpa, B. M., & Mythri, R. B. (2021) · IntechOpen eBooks · doi:10.5772/intechopen.97546 · Cited by 8
Choi, S.-I., Lee, G., Woo, J.-H., Jun, I., & Kim, E. K. (2023) · Genes · doi:10.3390/genes14030566 · Cited by 7
“For example, PGC1α and NRF2 levels were reduced under pathological conditions and are associated with mitochondrial dysfunction and oxidative stress [31,52,53].”
BackgroundOlkhova, E. A., Smith, L. A., Bradshaw, C., Gorman, G. S., Erskine, D., & Ng, Y. S. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24119698 · Cited by 7
Cui, D., Mesaros, A., Burdeos, G. C., Voigt, I., Giavalisco, P., Hinze, Y., Purrio, M., Neumaier, B., Drzezga, A. E., Obata, Y., et al. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21176297 · Cited by 7
“In order to generate dopaminergic neuron-specific Dnmt3a2/3L overexpression mouse cohorts (Dnmt3a2/3LDat/wt), the cre/loxp system (Supplementary Figure S1) was used to cross flox-Dnmt3a2/3L females [20] with Dat-cre males [21], and the offspring were further characterized by DAB”
Mitophagy could fight Parkinson’s disease through antioxidant action
Rita, A. D., & Strappazzon, F. (2019) · Reviews in the Neurosciences · doi:10.1515/revneuro-2018-0095 · Cited by 7
Salmani, B. Y., Lahti, L., Gillberg, L., Jacobsen, J. K., Mantas, I., Svenningsson, P., & Perlmann, T. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.06.05.543445 · Cited by 7
“Mouse lines and genotyping DatCre (Ekstrand et al., 2007), Pitx3GFP (Zhao et al.”
BackgroundMantas, I., Contestabile, A., Skara, V., Loiseau, C., Santos, I., Cramb, K. M. L., Filograna, R., Wade‐Martins, R., Magill, P. J., & Meletis, K. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.12.22.629963 · Cited by 12
Current and Emerging MR Methods and Outcome in Rodent Models of Parkinson’s Disease: A Review
Petiet, A. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.583678 · Cited by 6
“A conditional knockout mouse model with respiratory chaindeficient DA neurons was created in 2007 and named MitoPark mice (Ekstrand et al., 2007).”
BackgroundChen, Y.-H., Kuo, T., Wang, V., Cheng, P.-W., Huang, E. Y., Ma, K., Greig, N. H., Olson, L., Hoffer, B. J., & Tseng, K.-Y. (2024) · Journal of Parkinson s Disease · doi:10.3233/jpd-240080 · Cited by 6
“The breeding strategy employed to generate MP mice has been detailed in previous publications [32–34].”
Self-citationGenetic Models of Parkinson’s Disease
Kachidian, P., & Gubellini, P. (2020) · Neuromethods · doi:10.1007/978-1-0716-0912-5_3 · Cited by 6
A Drosophila model of mitochondrial disease phenotypic heterogeneity
Granat, L., Knorr, D. Y., Ranson, D. C., et al. (2024) · Biology Open · doi:10.1242/bio.060278 · Cited by 6
“Mitochondrial dysfunction is associated with perturbed mitochondrial morphology both in model systems and patients (Koopman et al., 2005; Ekstrand et al., 2007; Koopman et al., 2007).”
BackgroundZhang, J., & Darley-Usmar, V. M. (2011) · Springer eBooks · doi:10.1007/978-0-85729-701-3_6 · Cited by 7
Transcription factor Pitx3 mutant mice as a model for Parkinson’s disease
Zhou, F.-M., Li, L., Yue, J., & Dani, J. A. (2016) · Frontiers in Biology · doi:10.1007/s11515-016-1429-8 · Cited by 6
Thompson, L. H., & Björklund, A. (2009) · Progress in brain research · doi:10.1016/s0079-6123(09)17505-2 · Cited by 6
“Calbindin expression among mDA neurons has further significance in that it correlates with the cells that have the greatest capacity for survival in PD and a number of the associated animal models (German et al., 1992; Liang et al., 1996; Rodriguez et al., 2001; Maingay et al., 2006; Ekstrand et al., 2007).”
BackgroundTillack, K., Aboutalebi, H., & Kramer, E. R. (2015) · PLoS ONE · doi:10.1371/journal.pone.0136203 · Cited by 6
The Mitochondrial Connection in Parkinson's DiseasePreprint
Schon, E. A., Matheoud, D., & Przedborski, S. (2025) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a041891 · Cited by 7
Medeiros, D., Masini, D., Plewnia, C., et al. (2024) · Heliyon · doi:10.1016/j.heliyon.2024.e35948 · Cited by 5
“Immunofluorescence experiments were performed in Slc6a Cre (DAT-Cre) knock-in [24] crossed with loxP-flanked tdTomato mice (Jackson Laboratory, strain #007909).”
MethodDifferential synaptic depression mediates the therapeutic effect of deep brain stimulation
Li, J., Zhou, J., He, B., Papaneri, A. B., Kobzar, N. P., Yeh, A. C., Zhang, Y., & Cui, G. (2025) · Nature Neuroscience · doi:10.1038/s41593-025-02088-w · Cited by 6
“To further evaluate the therapeutic efficacy of the ‘chemogenetic DBS’ in a PD model that better resembles the symptoms in human patients, we used MitoPark mice 32 , a mouse PD model with a progressive loss of dopamine neurons and age-dependent motor deficits.”
Marzetti, E., Lorenzo, R. D., Calvani, R., Coelho‐Júnior, H. J., D’Argento, E., Pesce, V., Landi, F., Bucci, C., Guerra, F., & Picca, A. (2026) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2026.112167 · Cited by 8
Nutritionally Responsive PMv DAT Neurons Are Dynamically Regulated During Pubertal Transition
de Miera, C. S., Bellefontaine, N., Silveira, M. A., Fortin, C. N., Zampieri, T. T., Donato, J., Williams, K. W., Mendes‐da‐Silva, C., Heikkinen, L., Broberger, C., et al. (2025) · The FASEB Journal · doi:10.1096/fj.202500398r · Cited by 5
“Hypothalamic slices from adult DAT Cre ; tdTomato male [30], and female [31] mice were prepared, and the data were analyzed as previously described [22].”
Role of Oxidative Stress in the Etiology of Parkinson’s Disease: Advanced Therapeutic Products
Lavrova, A., Gretskaya, N. M., & Безуглов, В. В. (2021) · Russian Journal of Bioorganic Chemistry · doi:10.1134/s1068162021050307 · Cited by 5
Ketone ester–enriched diet ameliorates motor and dopamine release deficits in MitoPark mice
Mahajan, V. R., Nadel, J. A., King, M. T., Pawlosky, R. J., Davis, M. I., Veech, R. L., Lovinger, D. M., & Salinas, A. G. (2024) · European Journal of Neuroscience · doi:10.1111/ejn.16601 · Cited by 7
Sánchez-Ferrero, E., Coto, E., Estrada, M. B., Ribacoba, R., Guisasola, L. M., Salvador, C., & Álvarez, V. (2008) · Parkinsonism & Related Disorders · doi:10.1016/j.parkreldis.2008.09.004 · Cited by 5
“If these TFB1M/ TFB2M changes affect protein function, they could also affect mitochondrial replication/transcription or translation, increasing the risk for PD [11].”
BackgroundRole of Mitochondria in Neurodegenerative Diseases: The Dark Side of the “Energy Factory”
Correia, S. C., & Moreira, P. I. (2018) · Springer eBooks · doi:10.1007/978-3-319-73344-9_11 · Cited by 5
The Role of AlphαSynuclein in Mouse Models of Acute, Inflammatory and Neuropathic Pain
Möller, M., Möser, C. V., Weiss, U. M., & Niederberger, E. (2022) · Cells · doi:10.3390/cells11121967 · Cited by 5
“However, motor functions and learning ability do not differ from wild types [29].”
BackgroundMice Expressing Mutant Parkin Exhibit Hallmark Features of Parkinson's Disease
Hart, M. P., & Xu, A. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.1719-09.2009 · Cited by 5
Mitochondrial Proteins in the Development of Parkinson’s Disease
Zilocchi, M., Fasano, M., & Alberio, T. (2019) · Advances in experimental medicine and biology · doi:10.1007/978-981-13-8367-0_2 · Cited by 5
Shao, M., Zhao, C., Pan, Z., Yang, X., Cheng, G., Kam, G. H.-C., Zhou, H., & Lee, S. M. (2024) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2024.111224 · Cited by 5
Molinari, M., Aaltonen, A., Lieberman, O. J., Sulzer, D. L., Santini, E., & Borgkvist, A. (2025) · Science Advances · doi:10.1126/sciadv.adx4577 · Cited by 4
Crif1 deficiency in dopamine neurons triggers early-onset parkinsonism
Heo, J. Y., Park, A. H., Lee, M. J., Ryu, M. J., Kim, Y. K., Jang, Y. S., Kim, S., Shin, S., Son, H. J., Stein, T. D., et al. (2023) · Molecular Psychiatry · doi:10.1038/s41380-023-02234-5 · Cited by 4
Mitochondrial Dysfunction and Molecular Bases of Neurodegenerative Diseases
Kolesnikova, E. E. (2013) · Neurophysiology · doi:10.1007/s11062-013-9341-1 · Cited by 4
Spiny Projection Neuron Dynamics in Toxin and Transgenic Models of Parkinson’s Disease
Du, Y., & Graves, S. M. (2019) · Frontiers in Neural Circuits · doi:10.3389/fncir.2019.00017 · Cited by 4
Mitochondrial DNA alterations in aged macrophage migration inhibitory factor-knockout mice
Herbst, A. J., Hoang, A. N., Woo, W., McKenzie, D. I., Aiken, J. M., Miller, R. A., Allison, D. B., Liu, N., & Wanagat, J. (2019) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2019.111126 · Cited by 4
A Robotic Surgery Approach to Mitochondrial Transfer Amongst Single Cells
Shakoor, A., Xie, M., Pan, F., Gao, W., Sun, J., & Sun, D. B. (2019) · IEEE/RSJ International Conference on Intelligent Robots and Systems (IROS) · doi:10.1109/iros40897.2019.8968588 · Cited by 4
“For example, mitochondrial dysfunction has been associated with ageing and neurodegenerative disorders [4], [5] as well as epilepsy [6] and type 2 diabetes”
BackgroundSingle-Cell Approaches for Studying the Role of Mitochondrial DNA in Neurodegenerative Disease
Bailey, L. J., Elson, J. L., & Pienaar, I. S. (2021) · Methods in molecular biology · doi:10.1007/978-1-0716-1270-5_19 · Cited by 4
Mitochondrial dysfunction in Parkinson’s disease: a possible target for neuroprotection
Gleave, J. A., Perri, P. D., & Nash, J. E. (2014) · Frontiers in Biology · doi:10.1007/s11515-014-1337-8 · Cited by 5
“…“ MitoPark ” mice, which have a disrupted TFAM gene, demonstrated that loss of TFAM leads to an age-dependent development of parkinsonian-like symptoms including the formation of inclusions and loss of DA neurons (Ekstrand et al., 2007), further implicating mtDNA integrity to be important in PD.”
Recinto, S. J., Premachandran, S., Mukherjee, S., Allot, A., MacDonald, A., Yaqubi, M., Gruenheid, S., Trudeau, L., & Stratton, J. A. (2024) · European Journal of Neuroscience · doi:10.1111/ejn.16307 · Cited by 4
“…transgenic mice DAT-Cre transgenic lines are considered more reliable in the selective identification of midbrain DA neurons compared with other reporter mouse lines such as TH-Cre (Bäckman et al., 2006; Ekstrand et al., 2007; Engblom et al., 2008; Lindeberg et al., 2004; Zhuang et al., 2005).”
BackgroundShen, W., Zheng, M., Zhao, Y., Ni, F., & Zhu, X. (2025) · The FASEB Journal · doi:10.1096/fj.202501454rr · Cited by 3
“Subsequent studies constructed and characterized dopaminergic neuron-specific Tfam knockout mouse model that mirrored progressive PD phenotypes [20, 21], yet the possible mechanism remains to be explored.”
Schmidt, M. Y., Cuervo, A. M., Double, K. S., Ehninger, D., Goldberg, M. S., Harvey, K., Hoeijmakers, J. H. J., Luk, K. C., Mastroberardino, P. G., Moore, D. J., et al. (2026) · npj Parkinson s Disease · doi:10.1038/s41531-025-01239-x · Cited by 5
Abdalla, A., Padhi, P., Backes, N., Thyer, R. T., Zenitsky, G. D., Jin, H., Anantharam, V., Kanthasamy, A., Ellington, A. D., Phillips, G. J., et al. (2026) · ACS Synthetic Biology · doi:10.1021/acssynbio.5c00786 · Cited by 3
The central role of mitochondrial dysfunction in neurodegeneration: implications for therapy
Raafat, M. A., Al-Hasnaawei, S., Mousa, H. M., Hanumanthayya, M., Sahoo, S., Prathiba, S., Singh, G., & Sinha, A. (2026) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-026-05542-w · Cited by 6
“…dysfunction is induced specifically in dopaminergic neu - rons (for example, in MitoPark mice), some key motor and cognitive features are reproduced, a finding that illustrates how cell-type-dependent mitochondrial defects can drive disease-associated neurodegenerative phenotypes [61, 62].”
Introducing PIGMO, a novel PIGmented MOuse model of Parkinson’s disease
Chocarro, J., Maraña, S., Espelosin, M., Rico, A. J., Ariznabarreta, G., Lorenzo-Ramos, E., Ilarduya, M. M., Hernández-Alcoceba, R., Chillón, M., Vila, M., et al. (2026) · npj Parkinson s Disease · doi:10.1038/s41531-026-01289-9 · Cited by 3
Rahman, M. M., Sarker, M. T., Ahmed, S., Uddin, M. N., Islam, M. R., Islam, M. R., Das, S., Mukherjee, N., Hemeg, H. A., Rauf, A., et al. (2023) · Process Biochemistry · doi:10.1016/j.procbio.2023.07.007 · Cited by 4
Sex/Gender Differences in Parkinson’s Disease
Lee, J. (2024) · Springer eBooks · doi:10.1007/978-981-97-0130-8_26 · Cited by 3
Etiology and pathogenesis of Parkinson’s disease: role of mitochondrial pathology
Brini, M., Ottolini, & Calí, T. (2013) · Research and Reports in Biochemistry · doi:10.2147/rrbc.s28413 · Cited by 3
“45,74,75 In addition, dopaminergic neurons show a reduction in the mitochondrial mass compared to nondop-aminergic cells, which further contributes to mitochondrial dysfunctions.”
Bimpisidis, Z., König, N., & Wallén‐Mackenzie, Å. (2020) · Journal of Visualized Experiments · doi:10.3791/60867-v · Cited by 3
The Nigro-Striatal DA Neurons and Mechanisms of Their Degeneration in Parkinson’s Disease
Fuxé, K., Marcellino, D. J., Antonelli, T., et al. (2008) · doi:10.1093/acprof:oso/9780195369007.003.0007 · Cited by 3
McIver, E. L., Chu, H., Atherton, J. F., Cosgrove, K. E., Kondapalli, J., Wokosin, D. L., Surmeier, D. J., & Mark, D. B. (2018) · SSRN Electronic Journal · doi:10.1101/385443 · Cited by 4
“…striatal dopamine has fallen by >95% and the number of tyrosine-hydroxylase expressing SN DA neurons has fallen by >60 % (Ekstrand and Galter, 2009; Ekstrand et al., 2007), the frequency, regularity, and incidence of autonomous STN activity in slices from Mito-Park mice were significantly lower…”
BackgroundSalmani, B. Y., Lahti, L., Gillberg, L., Jacobsen, J. K., Mantas, I., Svenningsson, P., & Perlmann, T. (2024) · eLife · doi:10.7554/elife.89482.2 · Cited by 3
Xiao, X., Yeghiazaryan, G., Eggersmann, F. R., Cremer, A. L., Backes, H., Kloppenburg, P., & Hausen, A. C. (2023) · eLife · doi:10.7554/elife.91716.4 · Cited by 6
“…of tyrosine hydroxylase ( Th ), Ox1R ( Hcrtr1 ) and Ox2R ( Hcrtr2 ) in control (Ox1R fl/fl , DAT wt/wt ) mice and Ox1R ΔDAT (Ox1R fl/fl , DAT-Cre tg/wt ) mice, from the same breeding crossing mice carrying a loxP-flanked Ox1R-allele (Ox1R fl/fl ) with DAT-Cre tg/wt mice ( Ekstrand et al., 2007 ).”
Tzanoulinou, S., Astori, S., Grandi, L. C., Gullo, F., Kalusivikako, R., Rai, S., Limorenko, G., Tafti, M., Becchetti, A., & Vassalli, A. (2026) · Biological Psychiatry · doi:10.1016/j.biopsych.2026.05.022 · Cited by 5
Sharallah, O. A., Malakar, V. K., Salama, A. E., Elmaaz, S. M., Daba, S. A., & Poddar, N. K. (2026) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-026-01702-0 · Cited by 3
“…(DA) neurons of midbrain regions, causing Par-kinsonism phenotypic effects with late and early onset of progressive cognitive function impairment, followed by the intraneuronal inclusions formation dopaminergic neuronal death which is a major pathological hallmark in PD (Ekstrand et al. 2007).”
Khan, J., & Tatlı, I. İ. (2023) · Springer eBooks · doi:10.1007/978-981-99-3848-3_8 · Cited by 2
Targeting Mitochondria and Redox Dyshomeostasis in Brain Ageing: An Update
Cardoso, S., & Moreira, P. I. (2021) · Healthy ageing and longevity · doi:10.1007/978-3-030-84965-8_8 · Cited by 2
Modeling Mitochondrial Dysfunction in Neurodegenerative Disease
Komen, J. C., & Thorburn, D. R. (2011) · Springer eBooks · doi:10.1007/978-0-85729-701-3_12 · Cited by 2
Parkinson’s disease: towards better preclinical models and personalized treatments
Lindholm, D., Mäkelä, J., Liberto, V. D., et al. (2016) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-016-2141-1 · Cited by 2
Endogenous Defenses that Protect Dopamine Neurons
Leak, R. K., & Zigmond, M. J. (2008) · Elsevier eBooks · doi:10.1016/b978-0-12-374028-1.00013-0 · Cited by 2
Mitochondrial Neurodegenerative Disorders I: Parkinsonism and Cognitive Deficits
Ng, Y. S., Lax, N. Z., Bindoff, L. A., & Turnbull, D. M. (2019) · Springer eBooks · doi:10.1007/978-3-030-05517-2_14 · Cited by 2
Generating Mouse Models of Mitochondrial Disease
Ylikallio, E., & Tyynismaa, H. (2014) · Elsevier eBooks · doi:10.1016/b978-0-12-405195-9.00043-3 · Cited by 2
Paß, T., Ricke, K. M., Hofmann, P., Chowdhury, R., Nie, Y., Chinnery, P. F., Endepols, H., Neumaier, B., Carvalho, A. F., Rigoux, L., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.07.07.547791 · Cited by 2
Salmani, B. Y., Lahti, L., Gillberg, L., Jacobsen, J. K., Mantas, I., Svenningsson, P., & Perlmann, T. (2023) · eLife · doi:10.7554/elife.89482.1 · Cited by 2
Metadata
- Authors
- Ekstrand, M. I., Terzioglu, M., Galter, D., Zhu, S., Hofstetter, C., Lindqvist, E., Thams, S., Bergstrand, A., Hansson, F. S., Trifunovic, A., Hoffer, B., Cullheim, S., Mohammed, A. H., Olson, L., & Larsson, N.-G.
- Affiliations
- Karolinska University Hospital (SE)
- Department of Laboratory Medicine and
- Karolinska Institutet (SE)
- National Institutes of Health (US)
- Corresponding author
- Larsson, Nils-Göran
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2007-01-23
- Volume
- 104
- Issue
- 4
- Pages
- 1325-1330
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC1783140
- OpenAlex
- W2055557007
- Semantic Scholar
- eae41525f2f96b0fa42114d58d84dc3353e90137
- Cited by
- 605
- References
- 33
- Citations by year
- 2026: 20 · 2025: 25 · 2024: 35 · 2023: 32 · 2022: 25 · 2021: 33 · 2020: 40 · 2019: 34 · 2018: 38 · 2017: 28 · 2016: 19 · 2015: 32 · 2014: 31 · 2013: 32 · 2012: 29
- FWCI
- 23.38
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Michael J. Fox Foundation for Parkinson's Research
- Karolinska Institutet
- Vetenskapsrådet
- Swedish Brain Power
- National Institutes of Health
- U.S. Public Health Service
- Parkinsonfonden
- 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 › Nuclear Receptors and Signaling
- Keywords
- Parkinson's disease, mitochondrial dysfunction, respiratory chain deficiency, dopaminergic neurons, midbrain, Lewy bodies, TFAM, mitochondrial DNA mutations, conditional knockout mice, parkinsonism, motor impairment, intraneuronal inclusions
- MeSH terms
- Animals, Base Sequence, Dopamine, Electron Transport, Immunohistochemistry, Microscopy, Electron, Neurons, DNA Probes, In Situ Hybridization, Parkinsonian Disorders, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-10, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-10 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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