The DOI matches its Crossref record; 14 of the 14 references it cites were found in a registry or an index.
Enhancing Mitochondrial Calcium Buffering Capacity Reduces Aggregation of Misfolded SOD1 and Motor Neuron Cell Death without Extending Survival in Mouse Models of Inherited Amyotrophic Lateral Sclerosis
Open accessAbstract
Mitochondria have been proposed as targets for toxicity in amyotrophic lateral sclerosis (ALS), a progressive, fatal adult-onset neurodegenerative disorder characterized by the selective loss of motor neurons. A decrease in the capacity of spinal cord mitochondria to buffer calcium (Ca 2+) has been observed in mice expressing ALS-linked mutants of SOD1 that develop motor neuron disease with many of the key pathological hallmarks seen in ALS patients. In mice expressing three different ALS-causing SOD1 mutants, we now test the contribution of the loss of mitochondrial Ca 2+-buffering capacity to disease mechanism(s) by eliminating ubiquitous expression of cyclophilin D, a critical regulator of Ca 2+-mediated opening of the mitochondrial permeability transition pore that determines mitochondrial Ca 2+content. A chronic increase in mitochondrial buffering of Ca 2+in the absence of cyclophilin D was maintained throughout disease course and was associated with improved mitochondrial ATP synthesis, reduced mitochondrial swelling, and retention of normal morphology. This was accompanied by an attenuation of glial activation, reduction in levels of misfolded SOD1 aggregates in the spinal cord, and a significant suppression of motor neuron death throughout disease. Despite this, muscle denervation, motor axon degeneration, and disease progression and survival were unaffected, thereby eliminating mutant SOD1-mediated loss of mitochondrial Ca 2+buffering capacity, altered mitochondrial morphology, motor neuron death, and misfolded SOD1 aggregates, as primary contributors to disease mechanism for fatal paralysis in these models of familial ALS.
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Cites
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Baines, C. P., Kaiser, R. A., Purcell, N. H., Blair, N. S., Osinska, H., Hambleton, M. A., Brunskill, E. W., Sayen, M. R., Gottlieb, R. A., Dorn, G. W., et al. (2005) · Nature · doi:10.1038/nature03434 · Cited by 2,280
Inclusion body formation reduces levels of mutant huntingtin and the risk of neuronal death
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“Mitochondria isolated from CypD-null animals store significantly increased quantities of Ca 2 before mPTP opening (Baines et al., 2005; Basso et al., 2005; Nakagawa et al., 2005; Schinzel et al., 2005; Barsukova et al., 2011).”
BackgroundOnset and Progression in Inherited ALS Determined by Motor Neurons and Microglia
Boillée, S., Yamanaka, K., Lobsiger, C. S., Copeland, N. G., Jenkins, N. A., Kassiotis, G., Kollias, G., & Cleveland, D. W. (2006) · Science · doi:10.1126/science.1123511 · Cited by 1,623
Self-citationBruijn, L. I., Becher, M. W., Lee, M. K., Anderson, K. L., Jenkins, N. A., Copeland, N. G., Sisodia, S. S., Rothstein, J. D., Borchelt, D. R., Price, D. L., et al. (1997) · Neuron · doi:10.1016/s0896-6273(00)80272-x · Cited by 1,341
Self-citationAstrocytes expressing ALS-linked mutated SOD1 release factors selectively toxic to motor neurons
Nagai, M., Re, D. B., Nagata, T., Chalazonitis, A., Jessell, T. M., Wichterle, H., & Przedborski, S. (2007) · Nature Neuroscience · doi:10.1038/nn1876 · Cited by 1,220
Astrocytes as determinants of disease progression in inherited amyotrophic lateral sclerosis
Yamanaka, K., Chun, S. J., Boillee, S., Fujimori-Tonou, N., Yamashita, H., Gutmann, D. H., Takahashi, R., Misawa, H., & Cleveland, D. W. (2008) · Nature Neuroscience · doi:10.1038/nn2047 · Cited by 1,140 · cited 1×
“…is fully consistent with the now well accepted proposal that mutant SOD1mediated toxicity within astrocytes and microglia is a central component of the mechanism of disease progression (Beers et al., 2006; Boillée et al., 2006b; Di Giorgio et al., 2007; Nagai et al., 2007; Yamanaka et al., 2008).”
BackgroundSelf-citationNon–cell autonomous toxicity in neurodegenerative disorders: ALS and beyond
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Self-citationProperties of the Permeability Transition Pore in Mitochondria Devoid of Cyclophilin D
Basso, E., Fante, L., Fowlkes, J., Petronilli, V., Forte, M. A., & Bernardi, P. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.c500089200 · Cited by 808 · cited 6×
“…To determine whether increasing mitochondrial Ca 2 capacity alters SOD1 mutant-mediated ALS disease course and pathogenesis, we bred transgenic mice expressing mutant SOD1 mice that develop adult-onset fatal paralysis with Ppif / mice, which completely lack CypD expression (Basso et al., 2005).”
BackgroundInfluential
Cited by
Decoding ALS: from genes to mechanism
Taylor, J. P., Brown, R. H., & Cleveland, D. W. (2016) · Nature · doi:10.1038/nature20413 · Cited by 2,066
Self-citationThe machineries, regulation and cellular functions of mitochondrial calcium
Giorgi, C., Marchi, S., & Pinton, P. (2018) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-018-0052-8 · Cited by 941
Molecular mechanisms and consequences of mitochondrial permeability transition
Bonora, M., Giorgi, C., & Pinton, P. (2022) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-021-00433-y · Cited by 538
Agarwal, A., Wu, P.-H., Hughes, E. G., Fukaya, M., Tischfield, M. A., Langseth, A. J., Wirtz, D., & Bergles, D. E. (2017) · Neuron · doi:10.1016/j.neuron.2016.12.034 · Cited by 441
Zhu, Q., Jiang, J., Gendron, T. F., McAlonis-Downes, M., Jiang, L., Taylor, A., Diaz Garcia, S., Ghosh Dastidar, S., Rodriguez, M. J., King, P., et al. (2020) · Nature Neuroscience · doi:10.1038/s41593-020-0619-5 · Cited by 220
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Metadata
- Authors
- Parone, P. A., Da Cruz, S., Han, J. S., McAlonis-Downes, M., Vetto, A. P., Lee, S. K., Tseng, E., & Cleveland, D. W.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2013-03-13
- Volume
- 33
- Issue
- 11
- Pages
- 4657-4671
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- OpenAlex
- W2009976415
- Cited by
- 177
- References
- 14
- FWCI
- 14.82
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Parone, P. A., Da Cruz, S., Han, J. S., McAlonis-Downes, M., Vetto, A. P., Lee, S. K., Tseng, E., & Cleveland, D. W. (2013). Enhancing Mitochondrial Calcium Buffering Capacity Reduces Aggregation of Misfolded SOD1 and Motor Neuron Cell Death without Extending Survival in Mouse Models of Inherited Amyotrophic Lateral Sclerosis. The Journal of Neuroscience. https://doi.org/10.1523/jneurosci.1119-12.2013
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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