Inflammasome-derived cytokine IL18 suppresses amyloid-induced seizures in Alzheimer-prone mice
Open accessAbstract
Significance: Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by severe cognitive decline. The connection between neuroinflammation and the progressive loss of neurons is well known; however, the fact that most patients with AD suffer from concomitant seizure disorders is underappreciated. We have previously shown that the NLRP3 inflammasome, a major source of the proinflammatory cytokines IL1β and IL18, drives the pathology of AD in APP/PS1 mice. Here we report that surprisingly, IL18-deficient APP/PS1 mice develop a lethal seizure disorder due to an increase in neuronal network transmission. While targeting the NLRP3 inflammasome might be one potential method of halting AD progression, it should be recognized that specific cytokine inhibition in the brain may result in unintended deleterious consequences.
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Deletion of IL-18 is associated with lethal Picrotoxin-induced seizures in cerebral amyloidosis mice.
“Deletion of IL-18 is associated with lethal Picrotoxin-induced seizures in cerebral amyloidosis mice [71].”
From Microglia specific deletion of miR-155 in Alzheimer’s disease mouse models reduces amyloid-β pathology but causes hyperexcitability and seizures (2023) · cites this paper as [71]
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NLRP3 is activated in Alzheimer’s disease and contributes to pathology in APP/PS1 mice
Heneka, M. T., Kummer, M. P., Stutz, A., Delekate, A., Schwartz, S., Vieira-Saecker, A., Griep, A., Axt, D., Remus, A., Tzeng, T.-C., et al. (2013) · Nature · doi:10.1038/nature11729 · Cited by 2,898 · see citing works
Self-citationThe NALP3 inflammasome is involved in the innate immune response to amyloid-β
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Self-citationRegulation of NMDA receptor trafficking by amyloid-β
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The Postsynaptic Architecture of Excitatory Synapses: A More Quantitative View
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The case for rejecting the amyloid cascade hypothesis
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Inflammasomes in neuroinflammatory and neurodegenerative diseases
Voet, S., Srinivasan, S., Lamkanfi, M., & van Loo, G. (2019) · EMBO Molecular Medicine · doi:10.15252/emmm.201810248 · Cited by 761 · see citing works
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- Authors
- Tzeng, T.-C., Hasegawa, Y., Iguchi, R., Cheung, A., Caffrey, D. R., Thatcher, E. J., Mao, W., Germain, G., Tamburro, N. D., Okabe, S., Heneka, M. T., Latz, E., Futai, K., & Golenbock, D. T.
- Affiliations
- University of Bonn (DE)
- University of Massachusetts Chan Medical School (US)
- The University of Tokyo (JP)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2018-08-20
- Volume
- 115
- Issue
- 36
- Pages
- 9002-9007
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC6130368
- OpenAlex
- W2888194189
- Cited by
- 67
- References
- 9
- Citations by year
- 2026: 6 · 2025: 7 · 2024: 12 · 2023: 16 · 2022: 5 · 2021: 6 · 2020: 6 · 2019: 8 · 2018: 1
- FWCI
- 3.61
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Open Repository and Bibliography (University of Luxembourg) (submittedVersion, other-oa)
- eScholarship@UMassChan (submittedVersion)
- Funders
- Foundation for the National Institutes of Health (UL1-TR001453, R01NS085215)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Keywords
- IL-18, Alzheimer's disease, NLRP3 inflammasome, APP/PS1 mice, excitatory synaptic transmission, neuronal excitability, levetiracetam, neuroinflammation, amyloid-beta
- MeSH terms
- NLR Family, Pyrin Domain-Containing 3 Protein, Levetiracetam, Alzheimer Disease, Amyloid, Animals, Synaptic Transmission, Piracetam, Seizures, Mice, Knockout, Interleukin-18, Mice, Interleukin-1beta, Inflammasomes
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