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

被引：1978

作者：

Halle, Annett ^{[1
]}

Hornung, Veit ^{[1
]}

Petzold, Gabor C. ^{[2
,3
]}

Stewart, Cameron R. ^{[4
]}

Monks, Brian G. ^{[1
]}

Reinheckel, Thomas ^{[5
]}

Fitzgerald, Katherine A. ^{[1
]}

Latz, Eicke ^{[1
]}

Moore, Kathryn J. ^{[4
]}

Golenbock, Douglas T. ^{[1
]}

机构：

[1] Univ Massachusetts, Sch Med, Dept Immunol & Infect Dis, Worcester, MA 01605 USA

[2] Harvard Univ, Ctr Brain Sci, Cambridge, MA 02138 USA

[3] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA

[4] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Lipid Metab Unit, Boston, MA 02114 USA

[5] Univ Freiburg, Inst Mol Med & Cell Res, D-79104 Freiburg, Germany

来源：

NATURE IMMUNOLOGY | 2008年 / 9卷 / 08期

关键词：

D O I：

10.1038/ni.1636

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页码：857 / 865

页数：9

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