The NALP3 inflammasome is involved in the innate immune response to amyloid-β

By A. Halle, V. Hornung, G. Petzold, C. Stewart, Brian G. Monks, T. Reinheckel, Katherine A. Fitzgerald, E. Latz, K. Moore, D. Golenbock. Nature Immunology, 2008

1,957 citations recorded by the source corpus.

The fibrillar peptide amyloid-β (Aβ) has a chief function in the pathogenesis of Alzheimer's disease. Interleukin 1β (IL-1β) is a key cytokine in the inflammatory response to Aβ. Insoluble materials such as crystals activate the inflammasome formed by the cytoplasmic receptor NALP3, which results in the release of IL-1β. Here we identify the NALP3 inflammasome as a sensor of Aβ in a process involving the phagocytosis of Aβ and subsequent lysosomal damage and release of cathepsin B. Furthermore, the IL-1β pathway was essential for the microglial synthesis of proinflammatory and neurotoxic factors, and the inflammasome, caspase-1 and IL-1β were critical for the recruitment of microglia to exogenous Aβ in the brain. Our findings suggest that activation of the NALP3 inflammasome is important for inflammation and tissue damage in Alzheimer's disease.

Subfields: Immunology, Molecular Biology, Physiology

View Paper: https://www.semanticscholar.org/paper/28d97b63ba006af86c9589cf5fd165d92926d4e8

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Immunology

1. J. Tschopp
2. M. Lamkanfi
3. E. Latz
4. V. Dixit
5. Katherine A. Fitzgerald
6. Shizuo Akira
7. T. Mak
8. David Mcilwain

In Molecular Biology

1. J. Tschopp
2. M. Lamkanfi
3. V. Dixit
4. E. Latz
5. Katherine A. Fitzgerald
6. V. Deretic
7. J. Long
8. T. Kanneganti

In Physiology

1. J. Long
2. D. Holtzman
3. J. Tschopp
4. M. Lamkanfi
5. V. Dixit
6. C. Cunningham
7. M. Tan
8. L. Tan

Citations in the corpus

• NLRP3 inflammasome: From a danger signal sensor to a regulatory node of oxidative stress and inflammatory diseases (2015, methodology): “Different inflammasome complexes have been described to date.”
• Association of brain amyloidosis with pro-inflammatory gut bacterial taxa and peripheral inflammation markers in cognitively impaired elderly. (2017, background): “NLRP3 production has been found enhanced in the brain of AD patients (Halle et al., 2008; Martinon et al., 2009) and an NLRP3 inflammasome deficiency resulted in decreased pro-inflammatory cytokines release and decreased deposition of A β in the APP/PS1 animal model of AD (Heneka et al., 2013).”
• Cutting Edge: NF-κB Activating Pattern Recognition and Cytokine Receptors License NLRP3 Inflammasome Activation by Regulating NLRP3 Expression1 (2009, methodology): “Human ASC and NLRP3 were cloned from cDNA into the lentiviral plasmid FugW and immortalized macrophages were transduced as described (11).”
• Horror autoinflammaticus: the molecular pathophysiology of autoinflammatory disease (*). (2009, background): “Similarly, phagocytosis of amyloid-β in the central nervous system may also lead to lysosomal destabilization, inflammasome activation, and IL-1β release (137).”
• Inflammasomes in neuroinflammatory and neurodegenerative diseases (2019, background): “In vitro studies have shown that fibrillar Ab activates the NLRP3 inflammasome when phagocytosed by microglia, leading to activation of caspase-1 and release of IL-1b (Halle et al, 2008).”
• Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease (2020, background): “Notably, Aβ also can activate NF-κB signaling and the NLRP3-ASC inflammasome [426, 427], suggesting that Aβ and tau share common mechanisms in microglia activation.”