Article abstract


Nature Immunology 9, 857 - 865 (2008)
Published online: 11 July 2008 | doi:10.1038/ni.1636

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

Annett Halle1, Veit Hornung1, Gabor C Petzold2, Cameron R Stewart3, Brian G Monks1, Thomas Reinheckel4, Katherine A Fitzgerald1, Eicke Latz1, Kathryn J Moore3 & Douglas T Golenbock1


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

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  1. Department of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
  2. Center for Brain Science and Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
  3. Lipid Metabolism Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA.
  4. Institute for Molecular Medicine und Cell Research, Albert-Ludwigs University, Freiburg 79104, Germany.

Correspondence to: Douglas T Golenbock1 e-mail: douglas.golenbock@umassmed.edu



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