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PMID: 18604209 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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

Nature immunology ·Vol. 9 ·No. 8 ·2008-08-00 ·Pages 857-65

Halle A, Hornung V, Petzold GC, Stewart CR, Monks BG, Reinheckel T, Fitzgerald KA, Latz E, Moore KJ, Golenbock DT

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.

MeSH Terms
Alzheimer Disease/immunology Amyloid beta-Peptides/immunology Carrier Proteins/metabolism Immunity, Innate/immunology Inflammation/genetics,immunology,metabolism Inflammation Mediators/physiology NLR Family, Pyrin Domain-Containing 3 Protein
Chemicals
Amyloid beta-Peptides Carrier Proteins Inflammation Mediators NLR Family, Pyrin Domain-Containing 3 Protein NLRP3 protein, human
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Halle Annett
Department of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
Hornung Veit
Petzold Gabor C
Stewart Cameron R
Monks Brian G
Reinheckel Thomas
Fitzgerald Katherine A
Latz Eicke
Moore Kathryn J
Golenbock Douglas T
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Article Info
Journal
Nature immunology
Abbr.
Nat Immunol
ISSN
1529-2916
DOI
10.1038/ni.1636
Published
2008-08-00
Epub
2008-00-11
Pages
857-65
Language
English
Region
United States
NLM ID
100941354
PMCID
PMC3101478
Subset
IM
Grants
NIGMS NIH HHS · GM54060 · United States
NIAID NIH HHS · AI065483 · United States
NIGMS NIH HHS · R01 GM054060 · United States
NIGMS NIH HHS · R37 GM054060 · United States
NIAID NIH HHS · R01 AI065483 · United States
NIA NIH HHS · AG20255 · United States
NIA NIH HHS · R01 AG020255 · United States
NIA NIH HHS · R01 AG020255-06A1 · United States
Corrections
CommentIn
PMID: 18645588
External Links
PubMed source DOI: 10.1038/ni.1636 PMC Full Text View journal details
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