
Inflammasome signaling is dispensable for ß-amyloid-induced neuropathology in preclinical models of Alzheimer's disease
- Author
- Sahana Srinivasan, Daliya Kancheva, Sofie De Ren, Takashi Saito, Maude Jans (UGent) , Fleur Boone (UGent) , Charysse Vandendriessche (UGent) , Ine Paesmans, Herve Maurin, Roosmarijn Vandenbroucke (UGent) , Esther Hoste (UGent) , Sofie Voet, Isabelle Scheyltjens, Benjamin Pavie (UGent) , Saskia Lippens (UGent) , Marius Schwabenland, Marco Prinz, Takaomi Saido, Astrid Bottelbergs, Kiavash Movahedi, Mohamed Lamkanfi (UGent) and Geert van Loo (UGent)
- Organization
- Project
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- Investigating microglia inflammasome activation and regulation in Alzheimer disease
- Investigating itaconic acid as a critical immunometabolite in Influenza and RSV infections
- Study of the molecular pathways through which linear (de)ubiquitination governs skin inflammation and aberrant epidermal stem cell activation
- Study of microbiota-host interactions during colon cancer development using a unique microbiome dependent mouse model
- Host-microbe interaction in intestinal homeostasis: unravelling the mechanisms involved in the onset of multiple inflammation-related diseases
- Novel mechanisms of inflammation and cell death regulation in autoinflammatory and infectious diseases
- Cell Death Regulation and Role in Infection and Inflammatory Diseases
- Single cell analysis of inflammasome-mediated IL-1ß secretion in primary human monocytes
- Regulation of the Nlrp1a inflammasome in cutaneous and systemic autoinflammation
- Targeting NLRP3-mediated inflammation with novel chemotypes
- Abstract
- Background: Alzheimer’s disease (AD) is the most common neurodegenerative disorder affecting memory and cognition. The disease is accompanied by an abnormal deposition of ß-amyloid plaques in the brain that contributes to neurodegeneration and is known to induce glial inflammation. Studies in the APP/PS1 mouse model of ß-amyloid-induced neuropathology have suggested a role for inflammasome activation in ß-amyloid-induced neuroinflammation and neuropathology. Methods: Here, we evaluated the in vivo role of microglia-selective and full body inflammasome signalling in several mouse models of ß-amyloid-induced AD neuropathology. Results: Microglia-specific deletion of the inflammasome regulator A20 and inflammasome effector protease caspase-1 in the AppNL-G-F and APP/PS1 models failed to identify a prominent role for microglial inflammasome signalling in ß-amyloid-induced neuropathology. Moreover, global inflammasome inactivation through respectively full body deletion of caspases 1 and 11 in AppNL-G-F mice and Nlrp3 deletion in APP/PS1 mice also failed to modulate amyloid pathology and disease progression. In agreement, single-cell RNA sequencing did not reveal an important role for Nlrp3 signalling in driving microglial activation and the transition into disease-associated states, both during homeostasis and upon amyloid pathology. Conclusion: Collectively, these results question a generalizable role for inflammasome activation in preclinical amyloid-only models of neuroinflammation.
- Keywords
- Alzheimer's disease, ss-amyloid, microglia, neuroinflammation, inflammasome, NF-KAPPA-B, NLRP3 INFLAMMASOME, APOLIPOPROTEIN-E, COMMON VARIANTS, MOUSE MODELS, BETA, MICROGLIA, NEUROINFLAMMATION, ACTIVATION, PATHOLOGY
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Citation
Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-01HRQ9PRE73G83XMSQFJFJ53B7
- MLA
- Srinivasan, Sahana, et al. “Inflammasome Signaling Is Dispensable for SS-Amyloid-Induced Neuropathology in Preclinical Models of Alzheimer’s Disease.” FRONTIERS IN IMMUNOLOGY, vol. 15, 2024, doi:10.3389/fimmu.2024.1323409.
- APA
- Srinivasan, S., Kancheva, D., De Ren, S., Saito, T., Jans, M., Boone, F., … van Loo, G. (2024). Inflammasome signaling is dispensable for ß-amyloid-induced neuropathology in preclinical models of Alzheimer’s disease. FRONTIERS IN IMMUNOLOGY, 15. https://doi.org/10.3389/fimmu.2024.1323409
- Chicago author-date
- Srinivasan, Sahana, Daliya Kancheva, Sofie De Ren, Takashi Saito, Maude Jans, Fleur Boone, Charysse Vandendriessche, et al. 2024. “Inflammasome Signaling Is Dispensable for SS-Amyloid-Induced Neuropathology in Preclinical Models of Alzheimer’s Disease.” FRONTIERS IN IMMUNOLOGY 15. https://doi.org/10.3389/fimmu.2024.1323409.
- Chicago author-date (all authors)
- Srinivasan, Sahana, Daliya Kancheva, Sofie De Ren, Takashi Saito, Maude Jans, Fleur Boone, Charysse Vandendriessche, Ine Paesmans, Herve Maurin, Roosmarijn Vandenbroucke, Esther Hoste, Sofie Voet, Isabelle Scheyltjens, Benjamin Pavie, Saskia Lippens, Marius Schwabenland, Marco Prinz, Takaomi Saido, Astrid Bottelbergs, Kiavash Movahedi, Mohamed Lamkanfi, and Geert van Loo. 2024. “Inflammasome Signaling Is Dispensable for SS-Amyloid-Induced Neuropathology in Preclinical Models of Alzheimer’s Disease.” FRONTIERS IN IMMUNOLOGY 15. doi:10.3389/fimmu.2024.1323409.
- Vancouver
- 1.Srinivasan S, Kancheva D, De Ren S, Saito T, Jans M, Boone F, et al. Inflammasome signaling is dispensable for ß-amyloid-induced neuropathology in preclinical models of Alzheimer’s disease. FRONTIERS IN IMMUNOLOGY. 2024;15.
- IEEE
- [1]S. Srinivasan et al., “Inflammasome signaling is dispensable for ß-amyloid-induced neuropathology in preclinical models of Alzheimer’s disease,” FRONTIERS IN IMMUNOLOGY, vol. 15, 2024.
@article{01HRQ9PRE73G83XMSQFJFJ53B7, abstract = {{Background: Alzheimer’s disease (AD) is the most common neurodegenerative disorder affecting memory and cognition. The disease is accompanied by an abnormal deposition of ß-amyloid plaques in the brain that contributes to neurodegeneration and is known to induce glial inflammation. Studies in the APP/PS1 mouse model of ß-amyloid-induced neuropathology have suggested a role for inflammasome activation in ß-amyloid-induced neuroinflammation and neuropathology. Methods: Here, we evaluated the in vivo role of microglia-selective and full body inflammasome signalling in several mouse models of ß-amyloid-induced AD neuropathology. Results: Microglia-specific deletion of the inflammasome regulator A20 and inflammasome effector protease caspase-1 in the AppNL-G-F and APP/PS1 models failed to identify a prominent role for microglial inflammasome signalling in ß-amyloid-induced neuropathology. Moreover, global inflammasome inactivation through respectively full body deletion of caspases 1 and 11 in AppNL-G-F mice and Nlrp3 deletion in APP/PS1 mice also failed to modulate amyloid pathology and disease progression. In agreement, single-cell RNA sequencing did not reveal an important role for Nlrp3 signalling in driving microglial activation and the transition into disease-associated states, both during homeostasis and upon amyloid pathology. Conclusion: Collectively, these results question a generalizable role for inflammasome activation in preclinical amyloid-only models of neuroinflammation.}}, articleno = {{1323409}}, author = {{Srinivasan, Sahana and Kancheva, Daliya and De Ren, Sofie and Saito, Takashi and Jans, Maude and Boone, Fleur and Vandendriessche, Charysse and Paesmans, Ine and Maurin, Herve and Vandenbroucke, Roosmarijn and Hoste, Esther and Voet, Sofie and Scheyltjens, Isabelle and Pavie, Benjamin and Lippens, Saskia and Schwabenland, Marius and Prinz, Marco and Saido, Takaomi and Bottelbergs, Astrid and Movahedi, Kiavash and Lamkanfi, Mohamed and van Loo, Geert}}, issn = {{1664-3224}}, journal = {{FRONTIERS IN IMMUNOLOGY}}, keywords = {{Alzheimer's disease,ss-amyloid,microglia,neuroinflammation,inflammasome,NF-KAPPA-B,NLRP3 INFLAMMASOME,APOLIPOPROTEIN-E,COMMON VARIANTS,MOUSE MODELS,BETA,MICROGLIA,NEUROINFLAMMATION,ACTIVATION,PATHOLOGY}}, language = {{eng}}, pages = {{20}}, title = {{Inflammasome signaling is dispensable for ß-amyloid-induced neuropathology in preclinical models of Alzheimer's disease}}, url = {{http://doi.org/10.3389/fimmu.2024.1323409}}, volume = {{15}}, year = {{2024}}, }
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