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- Title
The NALP3 inflammasome is involved in the innate immune response to amyloid-beta.
- Authors
Halle, Annett; Hornung, Veit; Petzold, Gabor C; Stewart, Cameron R; Monks, Brian G; Reinheckel, Thomas; Fitzgerald, Katherine A; Latz, Eicke; Moore, Kathryn J; Golenbock, Douglas T
- Abstract
The fibrillar peptide amyloid-beta (A beta) has a chief function in the pathogenesis of Alzheimer's disease. Interleukin 1 beta (IL-1 beta) is a key cytokine in the inflammatory response to A beta. Insoluble materials such as crystals activate the inflammasome formed by the cytoplasmic receptor NALP3, which results in the release of IL-1 beta. Here we identify the NALP3 inflammasome as a sensor of A beta in a process involving the phagocytosis of A beta and subsequent lysosomal damage and release of cathepsin B. Furthermore, the IL-1 beta pathway was essential for the microglial synthesis of proinflammatory and neurotoxic factors, and the inflammasome, caspase-1 and IL-1 beta were critical for the recruitment of microglia to exogenous A beta in the brain. Our findings suggest that activation of the NALP3 inflammasome is important for inflammation and tissue damage in Alzheimer's disease.
- Publication
Nature immunology, 2008, Vol 9, Issue 8, p857
- ISSN
1529-2916
- Publication type
Journal Article
- DOI
10.1038/ni.1636