The DOI matches its Crossref record; 36 of the 36 references it cites were found in a registry or an index.
Conversion to the amyotrophic lateral sclerosis phenotype is associated with intermolecular linked insoluble aggregates of SOD1 in mitochondria
Open accessAbstract
Twenty percent of the familial form of amyotrophic lateral sclerosis (ALS) is caused by mutations in the Cu, Zn-superoxide dismutase gene ( SOD1 ) through the gain of a toxic function. The nature of this toxic function of mutant SOD1 has remained largely unknown. Here we show that WT SOD1 not only hastens onset of the ALS phenotype but can also convert an unaffected phenotype to an ALS phenotype in mutant SOD1 transgenic mouse models. Further analyses of the single- and double-transgenic mice revealed that conversion of mutant SOD1 from a soluble form to an aggregated and detergent-insoluble form was associated with development of the ALS phenotype in transgenic mice. Conversion of WT SOD1 from a soluble form to an aggregated and insoluble form also correlates with exacerbation of the disease or conversion to a disease phenotype in double-transgenic mice. This conversion, observed in the mitochondrial fraction of the spinal cord, involved formation of insoluble SOD1 dimers and multimers that are crosslinked through intermolecular disulfide bonds via oxidation of cysteine residues in SOD1. Our data thus show a molecular mechanism by which SOD1, an important protein in cellular defense against free radicals, is converted to aggregated and apparently ALS-associated toxic dimers and multimers by redox processes. These findings provide evidence of direct links among oxidation, protein aggregation, mitochondrial damage, and SOD1-mediated ALS, with possible applications to the aging process and other late-onset neurodegenerative disorders. Importantly, rational therapy based on these observations can now be developed and tested.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Rosen, D. R., Siddique, T., Patterson, D., Figlewicz, D. A., Sapp, P., Hentati, A., Donaldson, D., Goto, J., O'Regan, J. P., Deng, H.-X., et al. (1993) · Nature · doi:10.1038/362059a0 · Cited by 7,062
Self-citationMotor Neuron Degeneration in Mice that Express a Human Cu,Zn Superoxide Dismutase Mutation
Gurney, M. E., Pu, H., Chiu, A. Y., Dal Canto, M. C., Polchow, C. Y., Alexander, D. D., Caliendo, J., Hentati, A., Kwon, Y. W., Deng, H.-X., et al. (1994) · Science · doi:10.1126/science.8209258 · Cited by 4,143
Self-citationAmyotrophic Lateral Ssclerosis and Structural Defects in Cu,Zn Superoxide Dismutase
Deng, H.-X., Hentati, A., Tainer, J. A., Iqbal, Z., Cayabyab, A., Hung, W.-Y., Getzoff, E. D., Hu, P., Herzfeldt, B., Roos, R. P., et al. (1993) · Science · doi:10.1126/science.8351519 · Cited by 1,477
Self-citationDose-ranging study of riluzole in amyotrophic lateral sclerosis
Amyotrophic Lateral Sclerosis/Riluzole Study Group II, Lacomblez, L., Bensimon, G., Meininger, V, Leigh, P. N., & Guillet, P. (1996) · The Lancet · doi:10.1016/s0140-6736(96)91680-3 · Cited by 1,301
Reaume, A. G., Elliott, J. L., Hoffman, E. K., Kowall, N. W., Ferrante, R. J., Siwek, D. R., Wilcox, H. M., Flood, D. G., Beal, M. F., Brown, R. H., et al. (1996) · Nature Genetics · doi:10.1038/ng0596-43 · Cited by 1,292
Toxic Proteins in Neurodegenerative Disease
Taylor, J. P., Hardy, J., & Fischbeck, K. H. (2002) · Science · doi:10.1126/science.1067122 · Cited by 1,251
Aggregation and Motor Neuron Toxicity of an ALS-Linked SOD1 Mutant Independent from Wild-Type SOD1
Bruijn, L. I., Houseweart, M. K., Kato, S., Anderson, K. L., Anderson, S. D., Ohama, E., Reaume, A. G., Scott, R. W., & Cleveland, D. W. (1998) · Science · doi:10.1126/science.281.5384.1851 · Cited by 1,228
UNRAVELING THE MECHANISMS INVOLVED IN MOTOR NEURON DEGENERATION IN ALS
Bruijn, L. I., Miller, T. M., & Cleveland, D. W. (2004) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.27.070203.144244 · Cited by 1,185
Cellular Defenses against Unfolded Proteins
Sherman, M. Y., & Goldberg, A. L. (2001) · Neuron · doi:10.1016/s0896-6273(01)00177-5 · Cited by 991
Weisiger, R. A., & Fridovich, I. (1973) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)43969-0 · Cited by 895
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
Converging Mechanisms in ALS and FTD: Disrupted RNA and Protein Homeostasis
Ling, S.-C., Polymenidou, M., & Cleveland, D. W. (2013) · Neuron · doi:10.1016/j.neuron.2013.07.033 · Cited by 1,811
ALS: A Disease of Motor Neurons and Their Nonneuronal Neighbors
Boillée, S., Vande Velde, C., & Cleveland, D. W. (2006) · Neuron · doi:10.1016/j.neuron.2006.09.018 · Cited by 1,429
Mutations in UBQLN2 cause dominant X-linked juvenile and adult-onset ALS and ALS/dementia
Deng, H.-X., Chen, W., Hong, S.-T., Boycott, K. M., Gorrie, G. H., Siddique, N., Yang, Y., Fecto, F., Shi, Y., Zhai, H., et al. (2011) · Nature · doi:10.1038/nature10353 · Cited by 1,174
Self-citationMulti-target-Directed Ligands To Combat Neurodegenerative Diseases
Cavalli, A., Bolognesi, M. L., Minarini, A., Rosini, M., Tumiatti, V., Recanatini, M., & Melchiorre, C. (2008) · Journal of Medicinal Chemistry · doi:10.1021/jm7009364 · Cited by 1,152
Metadata
- Authors
- Deng, H.-X., Shi, Y., Furukawa, Y., Zhai, H., Fu, R., Liu, E., Gorrie, G. H., Khan, M. S., Hung, W.-Y., Bigio, E. H., Lukas, T., Dal Canto, M. C., O'Halloran, T. V., & Siddique, T.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2006-05-02
- Volume
- 103
- Issue
- 18
- Pages
- 7142-7147
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2099071260
- Cited by
- 431
- References
- 36
- FWCI
- 20.07
- Type
- journal article
- Language
- en
- Open access
- green
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.
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.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
How to cite
Cite CoChat for the checks on this page, and the paper for its own findings.
- This page
- CoChat. (2026). Citation check: Conversion to the amyotrophic lateral sclerosis phenotype is associated with intermolecular linked insoluble aggregates of SOD1 in mitochondria. https://app.cochat.ai/papers/10.1073/pnas.0602046103
- The paper
- Deng, H.-X., Shi, Y., Furukawa, Y., Zhai, H., Fu, R., Liu, E., Gorrie, G. H., Khan, M. S., Hung, W.-Y., Bigio, E. H., Lukas, T., Dal Canto, M. C., O'Halloran, T. V., & Siddique, T. (2006). Conversion to the amyotrophic lateral sclerosis phenotype is associated with intermolecular linked insoluble aggregates of SOD1 in mitochondria. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0602046103
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
