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

Autor: Halle, A., Hornung, V., Petzold, G., Stewart, C., Monks, B., Reinheckel, T., Fitzgerald, K., Latz, E., Moore, K., Golenbock, D.
Rok vydání: 2008
Zdroj: Nature Immunology
Popis: 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
Databáze: OpenAIRE