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).”
plaindirect- Asserted: passes — The authors put it forward as true.
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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.”
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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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In the paper
“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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The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
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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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
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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None of the sources cited for this claim have been checked yet.
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).
Cited by
Sorted by citations
Items 301–400 of 603
Wang, V., Kuo, T., Huang, E. Y., Ma, K., Chou, Y., Fu, Z.-Y., Lai, L.-W., Jung, J. H., Choi, H.-I., Choi, D., et al. (2021) · ACS Pharmacology & Translational Science · doi:10.1021/acsptsci.1c00013 · Cited by 35
Self-citationMitochondrial DNA homeostasis impairment and dopaminergic dysfunction: A trembling balance
Manini, A., Abati, E., Comi, G. P., Corti, S. P., & Ronchi, D. (2022) · Ageing Research Reviews · doi:10.1016/j.arr.2022.101578 · Cited by 36
Gatt, A. P., Jones, E. L., Francis, P. T., Ballard, C. G., & Bateman, J. E. (2013) · Neuroscience Letters · doi:10.1016/j.neulet.2013.10.045 · Cited by 36
Mouse models of oxidative phosphorylation dysfunction and disease
Vempati, U. D., Torraco, A., & Moraes, C. T. (2008) · Methods · doi:10.1016/j.ymeth.2008.09.008 · Cited by 33
Dopamine Release Dynamics in the Tuberoinfundibular Dopamine System
Stagkourakis, S., Dunevall, J., Taleat, Z., Ewing, A. G., & Broberger, C. (2019) · Journal of Neuroscience · doi:10.1523/jneurosci.2339-18.2019 · Cited by 36
“WT mice with C57BL/6J and BALB/c background were used, in addition to previously generated C57BL/6J Slc6a Cre (DAT-Cre) knock-in (Ekstrand et al., 2007) and floxed-tdTomato mice (The Jackson Laboratory, strain datasheet 007909).”
MethodHeterogeneity of dopamine release sites in health and degeneration
Lebowitz, J. J., & Khoshbouei, H. (2019) · Neurobiology of Disease · doi:10.1016/j.nbd.2019.104633 · Cited by 33
Viader, A., Wright-Jin, E. C., Vohra, B. P. S., Heuckeroth, R. O., & Milbrandt, J. (2011) · PLoS ONE · doi:10.1371/journal.pone.0027727 · Cited by 33
“Studies primarily focusing on the central nervous system (CNS) have established that mitochondrial dysfunction is involved in both the initiation and propagation of disease processes that eventually result in neuron death [12,13].”
BackgroundModelling Ser129 Phosphorylation Inhibits Membrane Binding of Pore-Forming Alpha-Synuclein Oligomers
Nübling, G., Levin, J., Bader, B., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0098906 · Cited by 32
Kim, M., Haroon, S., Chen, G., Ding, D., Wanagat, J., Liu, L., Zhang, Y., White, K., Park, H.-J., Han, C. J., et al. (2019) · Experimental Gerontology · doi:10.1016/j.exger.2019.110675 · Cited by 31
“With age, somatically derived mtDNA deletions clonally accumulate within a subset of individual cells (Wanagat et al., 2001; Ekstrand et al., 2007; McKiernan et al., 2007; Baris et al., 2015).”
BackgroundLangley, M. R., Ghaisas, S., Palanisamy, B. N., Ay, M., Jin, H., Anantharam, V., Kanthasamy, A., & Kanthasamy, A. G. (2021) · Experimental Neurology · doi:10.1016/j.expneurol.2021.113716 · Cited by 36
Jeong, S. H., Song, I. S., Kim, H. K., Lee, S. R., Song, S., Suh, H., Yoon, Y. G., Yoo, Y. H., Kim, N., Rhee, B. D., et al. (2012) · Molecules and Cells · doi:10.1007/s10059-012-0081-7 · Cited by 32
“…function, as well as for maintenance of proper mitochondrial copy number, mitochondrial morphology (Ekstrand et al., 2004; Kang et al., 2007; Larsson et al., 1998), and respiratory chain function (Ekstrand et al., 2004; 2007; Falkenberg et al., 2002; Ho et al., 2010; Larsson et al., 1998).”
BackgroundMitochondrial transcription factor A (TFAM) gene variation in Parkinson's disease
Álvarez, V., Corao, A. I., Sánchez-Ferrero, E., de Mena, L., Alonso‐Montes, C., Huerta, C., Estrada, M. B., Ribacoba, R., Guisasola, L. M., Salvador, C., et al. (2008) · Neuroscience Letters · doi:10.1016/j.neulet.2007.12.010 · Cited by 32
Progressive parkinsonism due to mitochondrial impairment: Lessons from the MitoPark mouse model
Beckstead, M. J., & Howell, R. D. (2021) · Experimental Neurology · doi:10.1016/j.expneurol.2021.113707 · Cited by 34
Negative transcriptional regulation of mitochondrial transcription factor A (TFAM) by nuclear TFAM
Lee, E. J., Kang, Y. C., Park, W., Jeong, J. H., & Pak, Y. K. (2014) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2014.05.082 · Cited by 30
Hidden phenotypes of PINK1/Parkin knockout mice
Paul, S., & Pickrell, A. M. (2021) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2021.129871 · Cited by 31
U-turn DNA bending by human mitochondrial transcription factor A
Rubio‐Cosials, A., & Solà, M. (2013) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2012.12.004 · Cited by 31
Mitochondrial Morphogenesis, Distribution, and Parkinson Disease
Yang, Y., & Lu, B. (2009) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e3181b2048c · Cited by 31
“Consistently, specific inactivation of TFAM in DA neurons has been reported to lead to defects in the oxidative phosphorylation pathway that result in a PD-like disease in mice (76).”
BackgroundMishra, A., Singh, S., Tiwari, V., Chaturvedi, S., Wahajuddin, M., & Shukla, S. (2019) · Neurochemistry International · doi:10.1016/j.neuint.2019.104463 · Cited by 32
Dillon, G. M., Shelton, D. S., McKinney, A. P., Caniga, M., Marcus, J., Ferguson, M. T., Kornecook, T. J., & Dodart, J. (2009) · Behavioural Brain Research · doi:10.1016/j.bbr.2009.04.036 · Cited by 30
Chen, C., Guderyon, M. J., Li, Y., Ge, G., Bhattacharjee, A., Ballard, C., He, Z., Masliah, E., Clark, R. A., O’Connor, J. C., et al. (2019) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2019.11.013 · Cited by 31
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
Mice with disrupted mitochondria used to model Parkinson’s disease
Doric, Z., & Nakamura, K. (2021) · Nature · doi:10.1038/d41586-021-02955-z · Cited by 28
Patki, G., & Lau, Y. (2011) · Neuroscience Letters · doi:10.1016/j.neulet.2011.10.036 · Cited by 30
Network oscillation rules imposed by species-specific electrical coupling
Stagkourakis, S., Pérez, C. T., Hellysaz, A., Ammari, R., & Broberger, C. (2018) · eLife · doi:10.7554/elife.33144 · Cited by 29
“Sprague Dawley rats (Charles River), DAT-Cre-tdTomato-floxed and DAT-Cre-GCaMP3floxed C57Bl/6J mice (own breeding – described in [Ekstrand et al., 2007]) were housed with ad libitum access to standard chow and tap water in a temperature-controlled environment under 12 hr light/dark conditions with…”
MethodMüller-Nedebock, A. C., Brennan, R. R., Venter, M., Pienaar, I. S., van der Westhuizen, F. H., Elson, J. L., Ross, O. A., & Bardien, S. (2019) · Neurochemistry International · doi:10.1016/j.neuint.2019.104495 · Cited by 30
Chronic A2A antagonist treatment alleviates parkinsonian locomotor deficiency in MitoPark mice
Marcellino, D. J., Lindqvist, E., Schneider, M., Müller, C. E., Fuxé, K., Olson, L., & Galter, D. (2010) · Neurobiology of Disease · doi:10.1016/j.nbd.2010.07.008 · Cited by 28
“…from a clinical trial of istradefylline as monotherapy in early PD,we used a genetic PDmodel, theMitoParkmouse, in which DA neurons undergo a slow and progressive degeneration due to the cell-type specific induction of mitochondrial dysfunction in midbrain DA neurons (Ekstrand et al., 2007).”
MethodSelf-citationMultimodal MRI Evaluation of the MitoPark Mouse Model of Parkinson’s Disease
Cong, L., Muir, E. R., Chen, C., Qian, Y., Liu, J., Biju, K. C., Clark, R. A., Li, S., & Duong, T. Q. (2016) · PLoS ONE · doi:10.1371/journal.pone.0151884 · Cited by 27
“The thalamus, which has connections with the basal ganglia and motor cortex, and hippocampus were also analyzed, both of which are reported to undergo atrophy in PD [31], although a previous study found that dopamine levels remain normal in the hippocampus of MitoPark mice [10].”
BackgroundMethodResultInfluentialMitochondria, Cellular Stress Resistance, Somatic Cell Depletion and Lifespan
Robb, E. L., Page, M. M., & Stuart, J. A. (2009) · Current Aging Science · doi:10.2174/1874609810902010012 · Cited by 27
“In these mice, disruption of mitochondrial transcription factor A specifically in dopaminergic neurons greatly reduces the efficiency of oxidative phosphorylation [158].”
Birla, H., Keswani, C., Singh, S. S., Zahra, W., Dilnashin, H., Rathore, A. S., Singh, R., Rajput, M., Keshri, P., & Singh, S. P. (2021) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.1c00481 · Cited by 28
Jackson, A., Engen, P. A., Forsyth, C. B., Shaikh, M. W., Naqib, A. D., Wilber, S., Frausto, D. M., Raeisi, S., Green, S. J., Bradaric, B. D., et al. (2022) · Frontiers in Neurology · doi:10.3389/fneur.2022.882628 · Cited by 27
“mitopark mouse model (98, 99) could all be considered for future studies.”
BackgroundParkinson’s Disease and Autophagy
Sánchez-Pérez, A. M., Clausell, B. C., Sanchez‐Andrés, J. V., & Herrero, M. T. (2012) · Parkinson s Disease · doi:10.1155/2012/429524 · Cited by 27
“However, whether proteasomal impairment is a key stepin familial or sporadic PD in which there are no primary defects in the ubiquitin-proteasome pathway is still not clear.”
BackgroundDelayed Dopamine Dysfunction and Motor Deficits in Female Parkinson Model Mice
Chen, Y.-H., Wang, V., Huang, E. Y., Chou, Y., Kuo, T., Olson, L., & Hoffer, B. J. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20246251 · Cited by 27
“The MitoPark model [24] allows for studies of the role of DA degeneration per se, studies of DA neuropathology, and behavioral effects over an extended time course [25–27].”
BackgroundMethodSelf-citationWang, Z., Chan, S.-W., Zhao, H., Miu, K.-K., & Chan, W. (2023) · 动物学研究 · doi:10.24272/j.issn.2095-8137.2022.406 · Cited by 28
Chu, Q., Luo, X., Zhan, X., Ren, Y., & Pang, H. (2015) · Scientific Reports · doi:10.1038/srep17170 · Cited by 26
Carbone, C., Costa, A., Provensi, G., Mannaioni, G., & Masi, A. (2017) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2017.00187 · Cited by 26
“…blockers ivabradine or ZD7288 causes a pattern of DAergic degeneration strikingly resembling that seen in MitoPark mice and MPP+-treated mice, two distinct PD models characterized by mitochondrial failure and SNpc-specific DAergic degeneration (Ekstrand et al., 2007; Blesa and Przedborski, 2014).”
BackgroundWu, C.-Y., Huang, R.-Y., Liao, E., Lin, Y., Ho, Y.-J., Chang, C., Chan, H., Huang, Y., Hsieh, T.-H., Fan, C., et al. (2020) · Brain stimulation · doi:10.1016/j.brs.2020.02.024 · Cited by 26
“2 Ultrasound-magnetic hybrid gene delivery improves PD syndrome 3 To examine whether PSp-MBs, FUS, and magnetic navig ation could reverse 4 neurodegeneration in mice, we selected the MitoPark mice with progressive 5 degeneration of dopaminergic neurons as the experim ental PD model [39].”
MethodLai, J.-H., Chen, K., Wu, J. C.-C., Olson, L., Brené, S., Huang, C.-Z., Chen, Y., Kang, S.-J., Ma, K., Hoffer, B. J., et al. (2019) · Brain Research · doi:10.1016/j.brainres.2019.146301 · Cited by 26
“We have previously reported that by 10-12 weeks of age MitoPark animals already show a significant reduction in overall motor activity and rotarod performance (Ekstrand et al., 2007).”
InfluentialSelf-citationParkinson’s Disease and the Gut: Future Perspectives for Early Diagnosis
Harsányiová, J., Buday, T., & Trancikova, A. K. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.00626 · Cited by 29
Kronenberg, G., Gertz, K. R., Overall, R. W., Harms, C., Klein, J., Page, M. M., Stuart, J. A., & Endres, M. (2011) · Experimental Neurology · doi:10.1016/j.expneurol.2011.01.014 · Cited by 25
“, 2002), Parkinson's disease (Duan et al., 2002; Ekstrand et al., 2007) and stroke (Endres et al.”
BackgroundIommarini, L., Peralta, S., Torraco, A., & Díaz, F. (2015) · Mitochondrion · doi:10.1016/j.mito.2015.01.008 · Cited by 28
Kao, C., Xu, M., Wang, L., Lin, S., Lee, H.-J., Duraine, L., Bellen, H. J., Goldstein, D. S., Tsai, S. Y., & Tsai, M. (2020) · PLoS Genetics · doi:10.1371/journal.pgen.1008868 · Cited by 25
“In order to examine whether elevated COUP-TFII expression can contribute to the disease progression of PD, we crossed OE mice with MitoPark mice, a progressive PD mouse model with impaired respiratory chain function in DA neurons [30].”
BackgroundMethodToskas, K., Salmani, B. Y., Skiteva, O., Pasławski, W., Gillberg, L., Skara, V., Antoniou, E., Södersten, E., Svenningsson, P., Chergui, K., et al. (2022) · Science Advances · doi:10.1126/sciadv.abo1543 · Cited by 27
Zhang, T. D., Kolbe, S., Beauchamp, L. C., Woodbridge, E., Finkelstein, D. I., & Burrows, E. L. (2022) · Biomedicines · doi:10.3390/biomedicines10123026 · Cited by 25
Mouse models of Parkinson's disease associated with mitochondrial dysfunction
Pickrell, A. M., Pinto, M., & Moraes, C. T. (2012) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2012.08.002 · Cited by 27
Frye, R. E., Rose, S., Wynne, R. A., Bennuri, S. C., Blossom, S. J., Gilbert, K. M., Heilbrun, L. P., & Palmer, R. F. (2017) · Scientific Reports · doi:10.1038/s41598-017-04821-3 · Cited by 25
Hartman, J. H., González-Hunt, C. P., Hall, S. M., Ryde, I. T., Caldwell, K. A., Caldwell, G. A., & Meyer, J. N. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20133202 · Cited by 26
“Genetic disruption of mitochondrial function also leads to dopaminergic neurodegeneration, including a mouse model with the mitochondrial transcription factor TFAM selectively silenced in dopaminergic neurons that shows progressive induction of mitochondrial dysfunction and nigral neuronal cell death as the animals re…”
BackgroundPinna, A., & Morelli, M. (2013) · Neurotoxicity Research · doi:10.1007/s12640-013-9446-8 · Cited by 24
“…mitochondrial dysfunction in midbrain dopaminergic neurons, a chronic treatment with the A2A antagonist MSX-3 prevented the reduction of spontaneous locomotor activity, demonstrating the potential efficacy of A2A antagonists as monotherapy in early PD (Ekstrand et al. 2007; Marcellino et al. 2010).”
Mitochondrial and Autophagic Regulation of Adult Neurogenesis in the Healthy and Diseased Brain
Büeler, H. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22073342 · Cited by 26
“It is likely that conditional Tfam knockout causes more severe mitochondrial defects than PINK1 deficiency, because Mito-Park mice with a Tfam deletion [61], but not PINK1-deficient mice [62], showed degenerative changes of the dopaminergic system.”
Backgroundl-Dopa induced dyskinesias in Parkinsonian mice: Disease severity or l-Dopa history
Shan, L., Díaz, Ó., Zhang, Y., et al. (2015) · Brain Research · doi:10.1016/j.brainres.2015.06.005 · Cited by 24
“By 33 weeks of age MitoPark mice have lost 70–80% of the nigral DA neurons, and present advanced parkinsonian symptoms (Ekstrand et al., 2007; Ekstrand and Galter, 2009; Galter et al., 2010).”
MethodInfluentialSelf-citationRubin, B. P., & Debnath, J. (2010) · Autophagy · doi:10.4161/auto.6.8.13430 · Cited by 24
α-Synuclein pathology and mitochondrial dysfunction: Toxic partners in Parkinson's disease
Mingo, Y. B., Galvis, M. L. E., & Henderson, M. X. (2025) · Neurobiology of Disease · doi:10.1016/j.nbd.2025.106889 · Cited by 30
“The selective deletion of either Ndufs2, a critical component of complex I (Gonz ´ alez-Rodríguez et al., 2021), or Tfam, a transcription factor essential for the expression of mtDNA (Ekstrand et al., 2007), in dopaminergic neurons leads to their progressive degeneration in mice.”
Frapin, M., Guignard, S., Meistermann, D., Grit, I., Moullé, V. S., Paillé, V., Parnet, P., & Amarger, V. (2020) · Nutrients · doi:10.3390/nu12051464 · Cited by 23
Paß, T., Aßfalg, M., Tolve, M., Blaess, S., Rothermel, M., Wiesner, R. J., & Ricke, K. M. (2020) · Molecular Neurobiology · doi:10.1007/s12035-020-01947-w · Cited by 24
“MitoPark mice are lacking TFAM exclusively in DaNs, which culminates in progressive neuronal death and corresponding motor impairment starting from 14 weeks of age [32, 33].”
BackgroundMethodInfluentialGawęda-Walerych, K., & Żekanowski, C. (2014) · Current Genomics · doi:10.2174/1389202914666131210211033 · Cited by 23
“For instance, a conditional SN-specific deletion of both mitochondrial transcription factor A (TFAM) alleles in mice leads to progressive motor dysfunction with adult onset, formation of intraneuronal inclusions, striatal dopamine depletion, death of DA neurons, abnormal mitochondrial morphology, reduced mtDNA express…”
BackgroundGermain, M., Nguyen, A. P., Khacho, M., Patten, D. A., Screaton, R. A., Park, D. S., & Slack, R. S. (2012) · Human Molecular Genetics · doi:10.1093/hmg/dds500 · Cited by 24
“These include ablation of complex I (Ndufs4) and complex IV (Cox10) subunits (6,7), as well as loss of the mitochondrial transcription factor A (8), all of which cause severe defects in oxidative phosphorylation (OXPHOS).”
BackgroundGPA protects the nigrostriatal dopamine system by enhancing mitochondrial function
Horváth, T. L., Erion, D. M., Elsworth, J. D., Roth, R. H., Shulman, G. I., & Andrews, Z. B. (2011) · Neurobiology of Disease · doi:10.1016/j.nbd.2011.03.005 · Cited by 23
Nielsen, B. E., & Ford, C. (2024) · Science Advances · doi:10.1126/sciadv.adp6301 · Cited by 24
Fatal attraction – The role of hypoxia when alpha-synuclein gets intimate with mitochondria
Burtscher, J., Syed, M. M. K., Keller, M. A., Lashuel, H. A., & Millet, G. P. (2021) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2021.07.017 · Cited by 25
“Genetically disrupted mitochondrial function in the mouse substantia nigra also results in PD-like pathology (Ekstrand et al., 2007).”
Fiore, N. J., Ganat, Y. M., Devkota, K., Batorsky, R., Lei, M., Lee, K., Cowen, L., Croft, G. F., Noggle, S., Nieland, T. J. F., et al. (2022) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-021-04047-7 · Cited by 26
Salmani, B. Y., Lahti, L., Gillberg, L., Jacobsen, J. K., Mantas, I., Svenningsson, P., & Perlmann, T. (2023) · eLife · doi:10.7554/elife.89482 · Cited by 46
Wang, V., Tseng, K.-Y., Kuo, T., Huang, E. Y., Lan, K.-L., Chen, Z., Ma, K., Greig, N. H., Jung, Y. J., Choi, H.-I., et al. (2024) · Journal of Biomedical Science · doi:10.1186/s12929-024-01025-6 · Cited by 23
“The breeding process for generating MP mice has been previously described [9, 15, 16].”
BackgroundMethodResultInfluentialSelf-citationPienaar, I. S., Lu, B., & Schallert, T. J. (2012) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2012.07.009 · Cited by 25
Proteomics as a new paradigm to tackle Parkinson’s disease research challenges
Licker, V., & Burkhard, P. R. (2014) · Translational Proteomics · doi:10.1016/j.trprot.2014.08.001 · Cited by 21
Mitochondria: Prospective Targets for Neuroprotection in Parkinson’s Disease
Yadav, A., Agarwal, S., Tiwari, S. K., & Chaturvedi, R. K. (2014) · Current Pharmaceutical Design · doi:10.2174/1381612820666140305224545 · Cited by 22
Zanon, A., Pramstaller, P. P., Hicks, A. A., & Pichler, I. (2018) · Parkinson s Disease · doi:10.1155/2018/8684906 · Cited by 21
“Interestingly, the MitoPark mouse, generated by direct deletion of mitochondrial transcription factor A (TFAM), which is needed for mtDNA replication, in DA neurons, is characterized by a marked deletion of mtDNA, impairment of oxidative phosphorylation, DA neuron degeneration, and motor deficits that mimic human park…”
BackgroundVaswani, A. R., Weykopf, B., Hagemann, C., Fried, H., Brüstle, O., & Blaess, S. (2019) · eLife · doi:10.7554/elife.41623 · Cited by 22
“The acetylation of tubulin contributes to the stabilization of tubulin (Fernández-Barrera and Alonso, 2018).”
BackgroundCabello-Rivera, D., Ortega‐Sáenz, P., Gao, L., Muñoz-Cabello, A. M., Bonilla, V., Schumacker, P. T., & López‐Barneo, J. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2202178119 · Cited by 21
Sleep and circadian rhythms in α‐synucleinopathies—Perspectives for disease modification
Kunz, D., Oster, H., Rawashdeh, O., Neumann, W., Münte, T. F., & Berg, D. (2023) · Acta Physiologica · doi:10.1111/apha.13966 · Cited by 24
Müller-Nedebock, A. C., van der Westhuizen, F. H., Kõks, S., & Bardien, S. (2021) · Movement Disorders · doi:10.1002/mds.28475 · Cited by 21
The reward value of sucrose in leptin-deficient obese mice
Domingos, A. I., Vaynshteyn, J., Sordillo, A., & Friedman, J. M. (2013) · Molecular Metabolism · doi:10.1016/j.molmet.2013.10.007 · Cited by 20
“Animals Dat-cre transgenic mice were obtained from the Laboratory of NilsGoran Larsson, Karolinska Institutet [6].”
MethodJia, Y., Li, J., Wang, Y., Ma, Y., Chen, L., Zhang, H., Xue, M., & Liang, H. (2024) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.3c06337 · Cited by 20
Gellhaar, S., Marcellino, D. J., Abrams, M. B., & Galter, D. (2015) · Genes Brain & Behavior · doi:10.1111/gbb.12210 · Cited by 20
“For the generation of MitoPark mice, see Ekstrand et al. (2007).”
Self-citationOXPHOS toxicogenomics and Parkinson's disease
López‐Gallardo, E., Iceta, R., Iglesias, E., Montoya, J., & Ruiz‐Pesini, E. (2011) · Mutation Research/Reviews in Mutation Research · doi:10.1016/j.mrrev.2011.06.004 · Cited by 19
Mitochondrial dysfunction in the striatum of aged chronic mouse model of Parkinson’s disease
Patki, G. (2009) · Frontiers in Aging Neuroscience · doi:10.3389/neuro.24.003.2009 · Cited by 20
Mitochondrial dysfunction in adult midbrain dopamine neurons triggers an early immune response
Filograna, R., Lee, S., Tiklová, K., Mennuni, M., Jonsson, V., Ringnér, M., Gillberg, L., Sopova, E., Shupliakov, O., Koolmeister, C., et al. (2021) · PLoS Genetics · doi:10.1371/journal.pgen.1009822 · Cited by 19
“In fact, mouse models with deletions [15] or depletion of mtDNA [16] selectively in midbrain DA neurons mirror the motor phenotypes and the typical neurodegeneration present in PD patients.”
BackgroundSelf-citationNeurodegenerative Diseases Associated with Mitochondrial DNA Mutations
Zhunina, O. A., Yabbarov, N. G., Grechko, A. V., Yet, S.-F., Sobenin, I. A., & Orekhov, A. N. (2020) · Current Pharmaceutical Design · doi:10.2174/1381612825666191122091320 · Cited by 19
Bal‐Price, A., Leist, M., Schildknecht, S., Monnet‐Tschudi, F., Paini, A., & Terron, A. (2018) · OECD series on adverse outcome pathways · doi:10.1787/b46c3c00-en · Cited by 22
Mitochondrial disfunction in Parkinson's disease
Бунеева, О. А., & Medvedev, A. E. (2011) · Biomeditsinskaya Khimiya · doi:10.18097/pbmc20115703246 · Cited by 18
What Role Does Mitochondrial Stress Play in Neurodegenerative Diseases?
Pickrell, A. M., & Moraes, C. T. (2010) · Methods in molecular biology · doi:10.1007/978-1-60761-756-3_4 · Cited by 18
Kv1.3 K + Channel Physiology Assessed by Genetic and Pharmacological Modulation
Varanita, T., Angi, B., Scattolini, V., & Szabó, I. (2022) · Physiology · doi:10.1152/physiol.00010.2022 · Cited by 20
Zhu, Y., Kohli, N., Young, A. J., Sheldon, M., Coni, J., Rajasekaran, M., Robinson, L., Chroneos, R., Riley, S., Guarnieri, J. W., et al. (2024) · Antioxidants · doi:10.3390/antiox13101226 · Cited by 18
Carbonell-Roig, J., Aaltonen, A., Wilson, K., Molinari, M., Cartocci, V., McGuirt, A. F., Mosharov, E. V., Kehr, J., Lieberman, O. J., Sulzer, D., et al. (2024) · Cell Reports · doi:10.1016/j.celrep.2024.114997 · Cited by 17
Zhou, T., Jin, Z., Jiang, R., & Li, W. (2025) · Frontiers in Pharmacology · doi:10.3389/fphar.2025.1600439 · Cited by 19
Yılmaz, A., Ashrafi, N., Ashrafi, R., Akyol, S., Saiyed, N., Kerševičiūtė, I., Gabrielaitė, M., Gordevičius, J., & Graham, S. F. (2025) · npj Parkinson s Disease · doi:10.1038/s41531-025-01023-x · Cited by 25
“Without confounding pharmacological effects research using the MitoPark model has con fi rmed sex-speci fi c differences in PD, with males exhibiting more severe symptoms and ovariectomized females displaying a similar disease progression as males 56,57 .”
Dopamine Neuron Challenge Test for early detection of Parkinson’s disease
Zhou, J., Li, J., Papaneri, A. B., Kobzar, N. P., & Cui, G. (2021) · npj Parkinson s Disease · doi:10.1038/s41531-021-00261-z · Cited by 18
Venkatesan, D., Iyer, M., Narayanasamy, A., Gopalakrishnan, A. V., & Vellingiri, B. (2023) · Molecular Neurobiology · doi:10.1007/s12035-023-03500-x · Cited by 17
“Certainly, TFAM knockout in DA neurons in MitoPark mice indicates decreased levels of mtDNA, and progressive DA degeneration [59].”
BackgroundAnorexia and Hypothalamic Degeneration
Nilsson, I. A. K., Lindfors, C., Schalling, M., Hökfelt, T. G. M., & Johansen, J. E. (2013) · Vitamins and hormones · doi:10.1016/b978-0-12-410473-0.00002-7 · Cited by 22
Anvret, A., Ran, C., Westerlund, M., Thelander, A.-C., Sydow, O., Lind, C., Håkansson, A. S., Nissbrandt, H., Galter, D., & Belin, A. C. (2010) · Parkinson s Disease · doi:10.4061/2010/491751 · Cited by 17
“Conditional knockout mice with a disruption of the mitochondrial transcription factor A (Tfam) in DA neurons (“MitoPark” mice) lend additional support to the hypothesis of mitochondrial involvement in PD [11].”
BackgroundSelf-citationAy, M., Charli, A., Langley, M. R., Jang, A.-Y., Padhi, P., Jin, H., Anantharam, V., Kalyanaraman, B., Kanthasamy, A., & Kanthasamy, A. G. (2024) · Frontiers in Neuroscience · doi:10.3389/fnins.2024.1356703 · Cited by 15
Modelling Mitochondrial Dysfunction in Mice
Doğan, Ş. A., & Trifunović, A. (2011) · Physiological Research · doi:10.33549/physiolres.932179 · Cited by 16
“Characterization of tissue-specific Tfam knockouts has demonstrated that TFAM deficiency leads to mtDNA depletion, reduction in levels of mitochondrial transcripts, and severe respiratory chain deficiency (Wang et al. 1999, Silva et al. 2000, Sorensen et al. 2001, Ekstrand et al. 2007).”
InfluentialSelf-citationOnaolapo, O. J., Onaolapo, A. Y., Olowe, O. A., Udoh, M. O., Udoh, D. O., & Nathaniel, I. T. (2019) · Current Neuropharmacology · doi:10.2174/1570159x18666191230114339 · Cited by 16
“This knowledge comes from studies that have associated mitochondrial oxidative injury, increased production of mitochondrial mutant proteins, and mitochondrial biogenesis with cellular alterations in neurodegenerative diseases [132-141].”
BackgroundAltered glutamate release in the dorsal striatum of the MitoPark mouse model of Parkinson's disease
Farrand, A. Q., Gregory, R. A., Bäckman, C. M., et al. (2016) · Brain Research · doi:10.1016/j.brainres.2016.09.025 · Cited by 16
Neuronal Mitophagy: Lessons from a Pathway Linked to Parkinson’s Disease
Corti, O. (2019) · Neurotoxicity Research · doi:10.1007/s12640-019-00060-8 · Cited by 18
Gan, Q., Ding, Y., Peng, M., Chen, L., Dong, J., Hu, J., & Ma, Y. (2023) · Biomolecules · doi:10.3390/biom13050873 · Cited by 17
“Furthermore, free dopamine inhibits the transition of α-syn from fibrils to mature fibrils, which leads to the accumulation of soluble fibrils in dopaminergic neurons, which is a hallmark of PD [64].”
BackgroundMitochondrial homeostasis regulation: A promising therapeutic target for Parkinson's disease
Yao, M., Dang, T., Wang, H., Zhu, X., & Chen, Q. (2023) · Behavioural Brain Research · doi:10.1016/j.bbr.2023.114811 · Cited by 15
“…and replication and acts as copy number controller, so TFAM mutations and single nucleotide polymorphism (SNPS) may also be associated with PD. Ekstrand et al., re-ported decreased mtDNA expression and the loss of DA neurons in MitoPark mice (conditional knockout of TFAM in DA neurons) [80].”
Maternal aggression driven by the transient mobilisation of a dormant hormone-sensitive circuit
Stagkourakis, S., Williams, P., Spigolon, G., Khanal, S., Ziegler, K., Heikkinen, L., Fisone, G., & Broberger, C. (2025) · Nature Communications · doi:10.1038/s41467-025-64043-4 · Cited by 17
Mitochondrial dysfunction and oxidative damage in the molecular pathology of Parkinson’s disease
Shadrina, M. I., & Slominsky, P. A. (2008) · Molecular Biology · doi:10.1134/s0026893308050099 · Cited by 15
Progressively disrupted somatodendritic morphology in dopamine neurons in a mouse Parkinson's model
Lynch, W. B., Tschumi, C. W., Sharpe, A. L., Branch, S. Y., Chen, C., Ge, G., Li, S., & Beckstead, M. J. (2018) · Movement Disorders · doi:10.1002/mds.27541 · Cited by 15
“Furthermore, dopamine neurons in MitoPark mice exhibit structurally altered mitochondria that are associated with the intracellular protein aggregates observed with this model.(10) Tfam is necessary for transcription initiation at mitochondrial promoters,(57) and its ablation leads to mitochondrial respiratory chain f…”
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Oxidative Stress in Parkinson's Disease
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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
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