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PubMed: 28019679

Title
Inflammasome activation and innate immunity in Alzheimer's disease.
Journal
Brain pathology (Zurich, Switzerland)
Volume
27
Issue
None
Pages
220-222
Date
2017-03-01
Authors
Heneka MT

Evidence 0bbe3552aa
JSON

Using a similar mouse model, Shi et al. treated animals with the antimalarial drug artemisinin, showing that this treatment results in inhibition of NFkB and presumably the NLRP3 inflammasome (13)

a(CHEBI:"(+)-artemisinin") decreases complex(GO:"NLRP3 inflammasome complex") View Subject | View Object

Appears in Networks:
Annotations
Confidence
High
MeSH
Neurons
NeuroMMSigDB
Nuclear factor Kappa beta subgraph

a(CHEBI:"(+)-artemisinin") decreases p(MGI:Nfkbia) View Subject | View Object

Appears in Networks:
Annotations
Confidence
High
MeSH
Neurons
NeuroMMSigDB
Nuclear factor Kappa beta subgraph

Evidence 59a19beec8
JSON

One of the canonical pathways of this innate immune response evoked by Abeta is the activation of the NOD-like receptor (NLR) family, pyrin domain containing 3 (NLRP3) inflammasome that became a focus of intense research

a(CHEBI:"amyloid-beta") increases bp(GO:"innate immune response") View Subject | View Object

Appears in Networks:
Annotations
Confidence
High
NeuroMMSigDB
Amyloidogenic subgraph
NeuroMMSigDB
Innate immune system subgraph

bp(GO:"innate immune response") increases act(complex(GO:"NLRP3 inflammasome complex")) View Subject | View Object

Appears in Networks:
Annotations
Confidence
High
NeuroMMSigDB
Amyloidogenic subgraph
NeuroMMSigDB
Innate immune system subgraph

Evidence 45ab01cddf
JSON

NLRP3 inflammasome activation results from TLR ligation and concomitant uptake of Ab in models of AD

a(CHEBI:"amyloid-beta") increases act(complex(GO:"NLRP3 inflammasome complex")) View Subject | View Object

Appears in Networks:
Annotations
Confidence
High
NeuroMMSigDB
Amyloidogenic subgraph

a(MESH:"Toll-Like Receptors") increases act(complex(GO:"NLRP3 inflammasome complex")) View Subject | View Object

Appears in Networks:
Annotations
Confidence
High
NeuroMMSigDB
Toll like receptor subgraph

Evidence 7075cabccc
JSON

NLRP3 inflammasome formation and subsequent activation of caspase-1 cleavage capacity was instrumental for Abeta-induced nitric oxide production and TNF-a release

a(CHEBI:"amyloid-beta") increases a(CHEBI:"nitric oxide") View Subject | View Object

Appears in Networks:
Annotations
Confidence
High
NeuroMMSigDB
Amyloidogenic subgraph
NeuroMMSigDB
Nitric oxide subgraph

a(CHEBI:"amyloid-beta") increases sec(p(HGNC:TNF)) View Subject | View Object

Appears in Networks:
Annotations
Confidence
High
NeuroMMSigDB
Amyloidogenic subgraph
NeuroMMSigDB
Tumor necrosis factor subgraph

complex(GO:"NLRP3 inflammasome complex") increases act(p(HGNC:CASP1)) View Subject | View Object

Appears in Networks:
Annotations
Confidence
High
NeuroMMSigDB
Caspase subgraph

complex(GO:"NLRP3 inflammasome complex") increases a(CHEBI:"nitric oxide") View Subject | View Object

Appears in Networks:
Annotations
Confidence
High
NeuroMMSigDB
Caspase subgraph
NeuroMMSigDB
Nitric oxide subgraph

complex(GO:"NLRP3 inflammasome complex") increases sec(p(HGNC:TNF)) View Subject | View Object

Appears in Networks:
Annotations
Confidence
High
NeuroMMSigDB
Amyloidogenic subgraph
NeuroMMSigDB
Tumor necrosis factor subgraph

act(p(HGNC:CASP1)) increases a(CHEBI:"nitric oxide") View Subject | View Object

Appears in Networks:
Annotations
Confidence
High
NeuroMMSigDB
Caspase subgraph
NeuroMMSigDB
Nitric oxide subgraph

act(p(HGNC:CASP1)) increases sec(p(HGNC:TNF)) View Subject | View Object

Appears in Networks:
Annotations
Confidence
High
NeuroMMSigDB
Caspase subgraph
NeuroMMSigDB
Tumor necrosis factor subgraph

Evidence 16e460d34e
JSON

Further data, showing “neuronal pyroptosis” of Abeta exposed neurons in a NLRP1- dependent and caspase-1-mediated manner may point to a vicious cycle, by which NLRP1 is causing neurodegeneration in response to increased Abeta production (14)

a(CHEBI:"amyloid-beta") increases act(complex(GO:"NLRP1 inflammasome complex")) View Subject | View Object

Appears in Networks:
Annotations
Confidence
High
MeSH
Neurons
NeuroMMSigDB
Amyloidogenic subgraph

a(CHEBI:"amyloid-beta") increases act(p(HGNC:CASP1)) View Subject | View Object

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Neurons
NeuroMMSigDB
Apoptosis signaling subgraph
NeuroMMSigDB
Caspase subgraph

complex(GO:"NLRP1 inflammasome complex") increases bp(GO:pyroptosis) View Subject | View Object

Appears in Networks:
Annotations
Confidence
High
MeSH
Neurons
NeuroMMSigDB
Apoptosis signaling subgraph

complex(GO:"NLRP1 inflammasome complex") increases bp(HBP:HBP00027) View Subject | View Object

Appears in Networks:
Annotations
Confidence
High
MeSH
Neurons
NeuroMMSigDB
Apoptosis signaling subgraph

act(p(HGNC:CASP1)) increases bp(GO:pyroptosis) View Subject | View Object

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Neurons
NeuroMMSigDB
Apoptosis signaling subgraph
NeuroMMSigDB
Caspase subgraph

Evidence 98c28d00d0
JSON

Using the herbizide, N,N0-dimethyl-4,40-bipyridinium dichloride (paraquat) as a mitochondrial toxin, which is known to induce oxidative stress, Chen et al. found increased levels of caspase-1 and IL-1b in brain of wild type and APP/PS1 transgenic mice (2), suggesting that those were due to NLRP3 inflammasome activation

a(CHEBI:paraquat) increases act(complex(GO:"NLRP3 inflammasome complex")) View Subject | View Object

Appears in Networks:
Annotations
Confidence
High
MeSH
Neurons
NeuroMMSigDB
Caspase subgraph

a(CHEBI:paraquat) increases p(HGNC:CASP1) View Subject | View Object

Appears in Networks:
Annotations
Confidence
High
MeSH
Neurons
NeuroMMSigDB
Caspase subgraph

a(CHEBI:paraquat) increases p(HGNC:IL1B) View Subject | View Object

Appears in Networks:
Annotations
Confidence
High
MeSH
Neurons
NeuroMMSigDB
Interleukin signaling subgraph

act(complex(GO:"NLRP3 inflammasome complex")) increases p(HGNC:IL1B) View Subject | View Object

Appears in Networks:
Annotations
Confidence
High
MeSH
Neurons
NeuroMMSigDB
Interleukin signaling subgraph

act(complex(GO:"NLRP3 inflammasome complex")) increases p(HGNC:CASP1) View Subject | View Object

Appears in Networks:
Annotations
Confidence
High
MeSH
Neurons
NeuroMMSigDB
Caspase subgraph

Evidence 8dee3ee6f2
JSON

Activation of the NLRP3 inflammasome by fibrillar Abeta has been described first by Halle et al. in 2008

a(HBP:HBP00038) increases act(complex(GO:"NLRP3 inflammasome complex")) View Subject | View Object

Appears in Networks:
Annotations
Confidence
High
NeuroMMSigDB
Amyloidogenic subgraph

Evidence 9362ed59d1
JSON

Recently, Kaushal et al. described the involvement of NLRP1 inflammasome activation in neurons. In these experiments, serum deprivation induced NLRP1-dependent caspase-1 activity and ASC speck formation, which resulted in caspase-6 activation and an increase in the Ab42/total Ab ratio (11)

complex(GO:"NLRP1 inflammasome complex") increases act(p(HGNC:CASP1)) View Subject | View Object

Appears in Networks:
Annotations
Confidence
High
NeuroMMSigDB
Caspase subgraph

act(complex(GO:"NLRP1 inflammasome complex")) increases act(p(HGNC:CASP6)) View Subject | View Object

Appears in Networks:
Annotations
Confidence
High
NeuroMMSigDB
Caspase subgraph

act(complex(GO:"NLRP1 inflammasome complex")) increases a(CHEBI:"amyloid-beta polypeptide 42") View Subject | View Object

Appears in Networks:
Annotations
Confidence
High
NeuroMMSigDB
Amyloidogenic subgraph

Evidence b2536463bd
JSON

Activation of NLRP3 leads to the generation of interleukin-1b (IL-1b) and interleukin 18 (IL-18), which are being cleaved by caspase-1 from their inactive precursors and subsequently

act(complex(GO:"NLRP3 inflammasome complex")) increases p(HGNC:IL1B) View Subject | View Object

Appears in Networks:
Annotations
Confidence
Medium
NeuroMMSigDB
Caspase subgraph
NeuroMMSigDB
Interleukin signaling subgraph

act(complex(GO:"NLRP3 inflammasome complex")) increases p(HGNC:IL18) View Subject | View Object

Appears in Networks:
Annotations
Confidence
Medium
NeuroMMSigDB
Caspase subgraph
NeuroMMSigDB
Interleukin signaling subgraph

p(HGNC:CASP1) increases act(p(HGNC:IL18)) View Subject | View Object

Appears in Networks:
Annotations
Confidence
Medium
NeuroMMSigDB
Caspase subgraph
NeuroMMSigDB
Interleukin signaling subgraph

p(HGNC:CASP1) increases act(p(HGNC:IL1B)) View Subject | View Object

Appears in Networks:
Annotations
Confidence
Medium
NeuroMMSigDB
Caspase subgraph
NeuroMMSigDB
Interleukin signaling subgraph

Evidence 0a6311323d
JSON

This finding was associated with spatial memory dysfunction and an increase in Abeta plaque deposition

act(complex(GO:"NLRP3 inflammasome complex")) decreases path(MESH:"Spatial Memory") View Subject | View Object

Appears in Networks:
Annotations
Confidence
High
MeSH
Neurons
NeuroMMSigDB
Amyloidogenic subgraph

act(complex(GO:"NLRP3 inflammasome complex")) increases a(CHEBI:"amyloid-beta") View Subject | View Object

Appears in Networks:
Annotations
Confidence
High
MeSH
Neurons
NeuroMMSigDB
Amyloidogenic subgraph

Evidence 0f066f7f51
JSON

Soluble Abeta (sAbeta)-induces NLRP3 inflammasome activation, however it requires the presence of the surface receptor CD36 (12)

composite(a(CHEBI:"amyloid-beta"), p(HGNC:CD36)) increases act(complex(GO:"NLRP3 inflammasome complex")) View Subject | View Object

Appears in Networks:
Annotations
Confidence
High
NeuroMMSigDB
Amyloidogenic subgraph

Evidence 1fd9bb5b8b
JSON

NLRP3 activation was characterized by ASC speck formation in an immune-activated microglial cell line and required a dual signal to become effective: the phagocytic uptake of Abeta and cathepsin B release after lysosomal disruption

composite(a(CHEBI:"amyloid-beta"), p(HGNC:CTSB)) increases act(complex(GO:"NLRP3 inflammasome complex")) View Subject | View Object

Appears in Networks:
Annotations
Confidence
High
NeuroMMSigDB
Amyloidogenic subgraph

Evidence 422b3bad7c
JSON

The combined effect of the increased IDE production and phagocytic Abeta clearance reduced the cerebral Abeta load substantially, even at late life. Since immunohistochemistry found NLRP3 exclusively expressed in microglial cells, it has been concluded that the observed changes were entirely due to NLRP3 inflammasome modulation in these cells

p(HGNC:IDE) decreases a(CHEBI:"amyloid-beta") View Subject | View Object

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Neurons
NeuroMMSigDB
Amyloidogenic subgraph
NeuroMMSigDB
Insulin signal transduction

p(HGNC:IDE) regulates complex(GO:"NLRP3 inflammasome complex") View Subject | View Object

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Neurons
NeuroMMSigDB
Amyloidogenic subgraph
NeuroMMSigDB
Insulin signal transduction

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