The DOI matches its Crossref record; 28 of the 28 references it cites were found in a registry or an index.
Mutant superoxide dismutase 1-induced IL-1β accelerates ALS pathogenesis
Open accessAbstract
ALS is a fatal motor neuron disease of adult onset. Neuroinflammation contributes to ALS disease progression; however, the inflammatory trigger remains unclear. We report that ALS–linked mutant superoxide dismutase 1 (SOD1) activates caspase-1 and IL-1β in microglia. Cytoplasmic accumulation of mutant SOD1 was sensed by an ASC containing inflammasome and antagonized by autophagy, limiting caspase-1–mediated inflammation. Notably, mutant SOD1 induced IL-1β correlated with amyloid-like misfolding and was independent of dismutase activity. Deficiency in caspase-1 or IL-1β or treatment with recombinant IL-1 receptor antagonist (IL-1RA) extended the lifespan of G93A- SOD1 transgenic mice and attenuated inflammatory pathology. These findings identify microglial IL-1β as a causative event of neuroinflammation and suggest IL-1 as a potential therapeutic target in ALS.
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Cites
Motor Neuron Degeneration in Mice that Express a Human Cu,Zn Superoxide Dismutase Mutation
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“These observations raise the possibility that mutant SOD1 is sensed by one ormultiple innate immune receptors that also account for the priming, analogously to the recognition of amyloid-β by an inflammasome and TLRs (5, 23, 24).”
BackgroundBruijn, 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
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Cited by
Ageing as a risk factor for neurodegenerative disease
Hou, Y., Dan, X., Babbar, M., Wei, Y., Hasselbalch, S. G., Croteau, D. L., & Bohr, V. A. (2019) · Nature Reviews Neurology · doi:10.1038/s41582-019-0244-7 · Cited by 3,310
Autophagy in immunity and inflammation
Levine, B., Mizushima, N., & Virgin, H. W. (2011) · Nature · doi:10.1038/nature09782 · Cited by 3,289
Treating inflammation by blocking interleukin-1 in a broad spectrum of diseases
Dinarello, C. A., Simon, A., & van der Meer, J. W. M. (2012) · Nature Reviews Drug Discovery · doi:10.1038/nrd3800 · Cited by 1,768
Microglia in neurodegeneration
Hickman, S., Izzy, S., Sen, P., Morsett, L., & El Khoury, J. (2018) · Nature Neuroscience · doi:10.1038/s41593-018-0242-x · Cited by 1,710
Innate immune activation in neurodegenerative disease
Heneka, M. T., Kummer, M. P., & Latz, E. (2014) · Nature Reviews Immunology · doi:10.1038/nri3705 · Cited by 1,437
Metadata
- Authors
- Meissner, F., Molawi, K., & Zychlinsky, A.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2010-07-20
- Volume
- 107
- Issue
- 29
- Pages
- 13046-13050
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2077331144
- Cited by
- 318
- References
- 28
- FWCI
- 9.55
- Type
- journal article
- Language
- en
- Open access
- green
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- Meissner, F., Molawi, K., & Zychlinsky, A. (2010). Mutant superoxide dismutase 1-induced IL-1β accelerates ALS pathogenesis. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.1002396107
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