The NALP3 inflammasome is involved in the innate immune response to amyloid-beta
Department of Medicine, Division of Infectious Diseases and Immunology
Alzheimer Disease; Amyloid beta-Peptides; Carrier Proteins; Immunity, Innate; Inflammation; Inflammation Mediators
Immunology and Infectious Disease
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.
DOI of Published Version
Nat Immunol. 2008 Aug;9(8):857-65. Epub 2008 Jul 11. Link to article on publisher's site
Halle, Annett; Hornung, Veit; Petzold, Gabor C.; Stewart, Cameron R.; Monks, Brian G.; Reinheckel, Thomas; Fitzgerald, Katherine A.; Latz, Eicke; Moore, Kathryn J.; and Golenbock, Douglas T., "The NALP3 inflammasome is involved in the innate immune response to amyloid-beta" (2008). Infectious Diseases and Immunology Publications and Presentations. 120.