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  3. PubMed:24561250

PubMed: 24561250

Title
The role of inflammasome in Alzheimer's disease.
Journal
Ageing research reviews
Volume
15
Issue
None
Pages
6-15
Date
2014-05-01
Authors
Chan C | Liu L

Evidence e8743b7d95
JSON

Activators include bacteria, virus, fungus, protoza, microbial proteins, crystalline urea, RNA, Alum, ATP, potassium efflux, fatty acids, Aβ, and most recently, degraded mitochondrial DNA (Liu et al., 2013a; Mathew et al., 2012; Schmidt and Lenz, 2012)

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

Appears in Networks:
Annotations
Confidence
High
NeuroMMSigDB
Amyloidogenic subgraph

a(CHEBI:"fatty acid") increases act(complex(GO:"inflammasome complex")) View Subject | View Object

Appears in Networks:
Annotations
Confidence
High

a(CHEBI:"potassium aluminium sulfate") increases act(complex(GO:"inflammasome complex")) View Subject | View Object

Appears in Networks:
Annotations
Confidence
High

a(CHEBI:"potassium(1+)") increases act(complex(GO:"inflammasome complex")) View Subject | View Object

Appears in Networks:
Annotations
Confidence
High

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

Appears in Networks:
Annotations
Confidence
High

deg(a(MESH:"DNA, Mitochondrial")) increases act(complex(GO:"inflammasome complex")) View Subject | View Object

Appears in Networks:
Annotations
Confidence
High

a(MESH:Bacteria) increases act(complex(GO:"inflammasome complex")) View Subject | View Object

Appears in Networks:
Annotations
Confidence
High

a(MESH:Fungi) increases act(complex(GO:"inflammasome complex")) View Subject | View Object

Appears in Networks:
Annotations
Confidence
High

a(MESH:RNA) increases act(complex(GO:"inflammasome complex")) View Subject | View Object

Appears in Networks:
Annotations
Confidence
High

a(MESH:Viruses) increases act(complex(GO:"inflammasome complex")) View Subject | View Object

Appears in Networks:
Annotations
Confidence
High

Evidence 885fcc1392
JSON

Phagocytosis and subsequent lysosomal damage trigger by Aβ initiate the activation of the NLRP3 inflammasome in the microglia (Halle et al., 2008)

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

Appears in Networks:
Annotations
Cell Ontology (CL)
microglial cell
Confidence
High
NeuroMMSigDB
Amyloidogenic subgraph

a(CHEBI:"amyloid-beta") decreases a(GO:lysosome) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
microglial cell
Confidence
High
NeuroMMSigDB
Amyloidogenic subgraph
NeuroMMSigDB
Endosomal lysosomal subgraph

a(GO:lysosome) decreases act(complex(GO:"NLRP3 inflammasome complex")) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
microglial cell
Confidence
High
NeuroMMSigDB
Amyloidogenic subgraph
NeuroMMSigDB
Endosomal lysosomal subgraph

bp(GO:phagocytosis) increases act(complex(GO:"NLRP3 inflammasome complex")) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
microglial cell
Confidence
High
NeuroMMSigDB
Amyloidogenic subgraph

Evidence f2ed427655
JSON

These studies highlighted the role of saturated fatty acids in the production of IL-1β by inflammasomes, i.e. NLRC4

a(CHEBI:"saturated fatty acid") increases p(HGNC:IL1B) View Subject | View Object

Appears in Networks:
Annotations
Confidence
High
NeuroMMSigDB
Interleukin signaling subgraph

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

Appears in Networks:
Annotations
Confidence
High
NeuroMMSigDB
Interleukin signaling subgraph

Evidence 0fd949d948
JSON

Spinal cord injury elevates extracellular ATP levels during neuroinflammation, which may act on purinergic receptors to trigger the activation of inflammasome (de Rivero Vaccari et al., 2012; Minkiewicz et al., 2013)

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

Appears in Networks:
Annotations
Confidence
Medium

path(MESH:"Spinal Cord Injuries") increases a(CHEBI:ATP) View Subject | View Object

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Extracellular Space

Evidence be38892d50
JSON

ATP, a danger-associated molecular pattern that is released from damaged cells after brain injury, activates the NLRP2 inflammasome, which consists of the NLRP2 receptor, ASC and caspase-1, in human astrocytes (Minkiewicz et al., 2013)

a(CHEBI:ATP) increases composite(complex(GO:"inflammasome complex"), p(HGNC:NLRP2)) View Subject | View Object

Appears in Networks:
Annotations
Confidence
High
NeuroMMSigDB
Caspase subgraph

p(HGNC:CASP1) association composite(complex(GO:"inflammasome complex"), p(HGNC:NLRP2)) View Subject | View Object

Appears in Networks:
Annotations
Confidence
High
NeuroMMSigDB
Caspase subgraph

p(HGNC:PYCARD) association composite(complex(GO:"inflammasome complex"), p(HGNC:NLRP2)) View Subject | View Object

Appears in Networks:
Annotations
Confidence
High
NeuroMMSigDB
Caspase subgraph

composite(complex(GO:"inflammasome complex"), p(HGNC:NLRP2)) association p(HGNC:NLRP2) View Subject | View Object

Appears in Networks:
Annotations
Confidence
High
NeuroMMSigDB
Caspase subgraph

composite(complex(GO:"inflammasome complex"), p(HGNC:NLRP2)) association p(HGNC:PYCARD) View Subject | View Object

Appears in Networks:
Annotations
Confidence
High
NeuroMMSigDB
Caspase subgraph

composite(complex(GO:"inflammasome complex"), p(HGNC:NLRP2)) association p(HGNC:CASP1) View Subject | View Object

Appears in Networks:
Annotations
Confidence
High
NeuroMMSigDB
Caspase subgraph

p(HGNC:NLRP2) association composite(complex(GO:"inflammasome complex"), p(HGNC:NLRP2)) View Subject | View Object

Appears in Networks:
Annotations
Confidence
High
NeuroMMSigDB
Caspase subgraph

Evidence 38ffd96116
JSON

The ATP-induced activation of the NLRP2 inflammasome interacts with the ATP-release pannexin 1 channel and ATP-gated P2X7 receptor leading to the maturation of IL-1β (Minkiewicz et al., 2013)

a(CHEBI:ATP) increases composite(complex(GO:"inflammasome complex"), p(HGNC:NLRP2)) View Subject | View Object

Appears in Networks:
Annotations
Confidence
High
NeuroMMSigDB
Interleukin signaling subgraph

composite(complex(GO:"inflammasome complex"), p(HGNC:NLRP2), p(HGNC:P2RX7), p(HGNC:PANX1)) increases p(HGNC:IL1B) View Subject | View Object

Appears in Networks:
Annotations
Confidence
High
NeuroMMSigDB
Interleukin signaling subgraph

Evidence 62836a53a0
JSON

In human astrocytes, ATP released from damaged or dying cells after traumatic brain injury activates the NLRP2 inflammasome, leading to the maturation of both IL-1β and IL-18 (Minkiewicz et al., 2013)

a(CHEBI:ATP) increases composite(complex(GO:"inflammasome complex"), p(HGNC:NLRP2)) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
astrocyte
Confidence
Medium
NeuroMMSigDB
Interleukin signaling subgraph

bp(GO:"cell death") increases sec(a(CHEBI:ATP)) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
astrocyte
Confidence
Medium
NeuroMMSigDB
Interleukin signaling subgraph

composite(complex(GO:"inflammasome complex"), p(HGNC:NLRP2)) increases p(HGNC:IL1B) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
astrocyte
Confidence
Medium
NeuroMMSigDB
Interleukin signaling subgraph

composite(complex(GO:"inflammasome complex"), p(HGNC:NLRP2)) increases p(HGNC:IL18) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
astrocyte
Confidence
Medium
NeuroMMSigDB
Interleukin signaling subgraph

path(MESH:"Brain Injuries, Traumatic") increases bp(GO:"cell death") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
astrocyte
Confidence
Medium
NeuroMMSigDB
Interleukin signaling subgraph

Evidence ccc9727bf0
JSON

In addition, Brilliant Blue G (BBG), a P2X7 receptor antagonist, inhibits ATP-induced activation of the NLRP2 inflammasome in human astrocytes (Minkiewicz et al., 2013)

a(CHEBI:ATP) increases composite(complex(GO:"inflammasome complex"), p(HGNC:NLRP2)) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
astrocyte
Confidence
Medium

a(PUBCHEM:6324599) decreases composite(complex(GO:"inflammasome complex"), p(HGNC:NLRP2)) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
astrocyte
Confidence
Medium

a(PUBCHEM:6324599) decreases act(p(HGNC:P2RX7)) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
astrocyte
Confidence
Medium

Evidence 35c9fe13d9
JSON

Palmitate, a fatty acid, activates the NLRC4 inflammasome in primary astrocytes leading to the release of IL-1β (Liu and Chan, 2014)

a(CHEBI:hexadecanoate) increases complex(GO:"IPAF inflammasome complex") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
astrocyte
Confidence
High
NeuroMMSigDB
Interleukin signaling subgraph

complex(GO:"IPAF inflammasome complex") increases sec(p(HGNC:IL1B)) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
astrocyte
Confidence
High
NeuroMMSigDB
Interleukin signaling subgraph

Evidence 05fa522854
JSON

Recently we identify that palmitate activates the NLRC4 inflammasome in primary astrocytes to release IL-1β, and ASC participates in the activation of the NLRC4 inflammasome (Liu and Chan, 2014)

a(CHEBI:hexadecanoate) increases act(complex(GO:"IPAF inflammasome complex")) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
astrocyte
Confidence
Medium
NeuroMMSigDB
Interleukin signaling subgraph

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

Appears in Networks:
Annotations
Cell Ontology (CL)
astrocyte
Confidence
Medium
NeuroMMSigDB
Interleukin signaling subgraph

p(HGNC:PYCARD) increases act(complex(GO:"IPAF inflammasome complex")) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
astrocyte
Confidence
Medium
NeuroMMSigDB
Caspase subgraph

Evidence f4111cb6d5
JSON

Probenecid, an inhibitor of pannexin 1, has been shown to significantly inhibit the expression and activation of the NLRP2 inflammasome, and the maturation of bothIL-1β and IL-18 in human astrocytes induced by ATP (Minkiewicz et al., 2013)

a(CHEBI:probenecid) decreases p(HGNC:PANX1) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
astrocyte
Confidence
Medium

a(CHEBI:probenecid) decreases composite(complex(GO:"inflammasome complex"), p(HGNC:NLRP2)) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
astrocyte
Confidence
Medium

a(CHEBI:probenecid) decreases p(HGNC:IL1B) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
astrocyte
Confidence
Medium
NeuroMMSigDB
Interleukin signaling subgraph

a(CHEBI:probenecid) decreases p(HGNC:IL18) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
astrocyte
Confidence
Medium
NeuroMMSigDB
Interleukin signaling subgraph

p(HGNC:PANX1) increases composite(complex(GO:"inflammasome complex"), p(HGNC:NLRP2)) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
astrocyte
Confidence
Medium

p(HGNC:PANX1) increases p(HGNC:IL1B) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
astrocyte
Confidence
Medium
NeuroMMSigDB
Interleukin signaling subgraph

p(HGNC:PANX1) increases p(HGNC:IL18) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
astrocyte
Confidence
Medium
NeuroMMSigDB
Interleukin signaling subgraph

Evidence ae176bfc52
JSON

Probenecid has also been demonstrated to reduce the activation of the NLRP1 inflammasome, and improve the learning performance in age-related cognitive decline (Mawhinney et al., 2011)

a(CHEBI:probenecid) decreases act(complex(GO:"NLRP1 inflammasome complex")) View Subject | View Object

Appears in Networks:
Annotations
Confidence
High

a(CHEBI:probenecid) increases bp(GO:learning) View Subject | View Object

Appears in Networks:
Annotations
Confidence
High

Evidence d3b7411ada
JSON

In vivo and cell studies demonstrate that fibrillar Aβ activates the NLRP3 inflammasome which is composed of the NLRP3 receptor, ASC and caspase-1, to produce IL-1β in microglia (Halle et al., 2008)

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

Appears in Networks:
Annotations
Cell Ontology (CL)
microglial cell
Confidence
Medium
NeuroMMSigDB
Amyloidogenic subgraph

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

Appears in Networks:
Annotations
Cell Ontology (CL)
microglial cell
Confidence
Medium
NeuroMMSigDB
Amyloidogenic subgraph

Evidence aa110a6829
JSON

In response to danger signals, inflammasomes assemble by self-oligomerizing the NLRs through interactions with the NACHT domain (van de Veerdonk et al., 2011)

a(MESH:"Pathogen-Associated Molecular Pattern Molecules") increases complex(GO:"inflammasome complex") View Subject | View Object

Appears in Networks:
Annotations
Confidence
High

a(MESH:Alarmins) increases complex(GO:"inflammasome complex") View Subject | View Object

Appears in Networks:
Annotations
Confidence
High

complex(a(MESH:"NLR Proteins"), p(INTERPRO:"NACHT-associated domain")) increases complex(GO:"inflammasome complex") View Subject | View Object

Appears in Networks:
Annotations
Confidence
High

Evidence 61dd468e46
JSON

The activators of the inflammasomes can be divided into two categories; pathogen associated molecular patterns (PAMPs) activate a host-defense reaction, and damage associated molecular patterns (DAMPs) activate a self-defense mechanism in response to danger signals (Salminen et al., 2008)

a(MESH:"Pathogen-Associated Molecular Pattern Molecules") increases act(complex(GO:"inflammasome complex")) View Subject | View Object

Appears in Networks:
Annotations
Confidence
High

a(MESH:Alarmins) increases act(complex(GO:"inflammasome complex")) View Subject | View Object

Appears in Networks:
Annotations
Confidence
High

Evidence 84f104c12c
JSON

Aging, another risk factor of AD, has been found to activate the NLRP1 inflammasome and upregulate IL-18 and IL-1β levels in the hippocampus of aged mice (Mawhinney et al., 2011)

bp(GO:aging) positiveCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Hippocampus
NeuroMMSigDB
Interleukin signaling subgraph

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

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Hippocampus
NeuroMMSigDB
Interleukin signaling subgraph

bp(GO:aging) increases p(HGNC:IL1B) View Subject | View Object

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Hippocampus
NeuroMMSigDB
Interleukin signaling subgraph

bp(GO:aging) increases p(HGNC:IL18) View Subject | View Object

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Hippocampus
NeuroMMSigDB
Interleukin signaling subgraph

path(MESH:"Alzheimer Disease") positiveCorrelation bp(GO:aging) View Subject | View Object

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Hippocampus
NeuroMMSigDB
Interleukin signaling subgraph

Evidence 025137932f
JSON

In the CNS, the production of IL-1β by inflammasomes, specifically NLRP1, NLRP2, NLRP3 and NLRC4, is well-characterized as compared to other interleukins (Minkiewicz et al., 2013; Trendelenburg, 2008)

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

Appears in Networks:
Annotations
Confidence
High
MeSH
Central Nervous System
NeuroMMSigDB
Interleukin signaling subgraph

complex(GO:"NLRP1 inflammasome complex") increases p(HGNC:IL1B) View Subject | View Object

Appears in Networks:
Annotations
Confidence
High
MeSH
Central Nervous System
NeuroMMSigDB
Interleukin signaling subgraph

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

Appears in Networks:
Annotations
Confidence
High
MeSH
Central Nervous System
NeuroMMSigDB
Interleukin signaling subgraph

composite(complex(GO:"inflammasome complex"), p(HGNC:NLRP2)) increases p(HGNC:IL1B) View Subject | View Object

Appears in Networks:
Annotations
Confidence
High
MeSH
Central Nervous System
NeuroMMSigDB
Interleukin signaling subgraph

Evidence bbf5339a61
JSON

In addition, NLRC4 and ASC levels are upregulated in the brains of AD patients (Liu and Chan, 2014), suggesting a possible role of the NLRC4 inflammasome in AD pathogenesis

complex(GO:"IPAF inflammasome complex") association path(MESH:"Alzheimer Disease") View Subject | View Object

Appears in Networks:
Annotations
Confidence
Medium
NeuroMMSigDB
Caspase subgraph

p(HGNC:PYCARD) positiveCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

Appears in Networks:
Annotations
Confidence
Medium
NeuroMMSigDB
Caspase subgraph

p(HGNC:NLRC4) positiveCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

Appears in Networks:
Annotations
Confidence
Medium
NeuroMMSigDB
Caspase subgraph

path(MESH:"Alzheimer Disease") positiveCorrelation p(HGNC:PYCARD) View Subject | View Object

Appears in Networks:
Annotations
Confidence
Medium
NeuroMMSigDB
Caspase subgraph

path(MESH:"Alzheimer Disease") positiveCorrelation p(HGNC:NLRC4) View Subject | View Object

Appears in Networks:
Annotations
Confidence
Medium
NeuroMMSigDB
Caspase subgraph

path(MESH:"Alzheimer Disease") association complex(GO:"IPAF inflammasome complex") View Subject | View Object

Appears in Networks:
Annotations
Confidence
Medium
NeuroMMSigDB
Caspase subgraph

Evidence 821e892b05
JSON

Spinal cord injury can activate the NLRP1 inflammasome to produce IL-1β in rat spinal cord neurons (de Rivero Vaccari et al., 2008)

act(complex(GO:"NLRP1 inflammasome complex")) increases p(HGNC:IL1B) View Subject | View Object

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

path(MESH:"Spinal Cord Injuries") increases act(complex(GO:"NLRP1 inflammasome complex")) View Subject | View Object

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

Evidence 837f1be19b
JSON

Spinal cord injury causes IL-18 and IL-1β release from neuronal cells through the activation of the NLRP1 inflammasome, composed of receptor NLRP1, adaptor protein ASC, caspase-1, caspase-11 and X-linked inhibitor of apoptosis protein (de Rivero Vaccari et al., 2008)

act(complex(GO:"NLRP1 inflammasome complex")) increases sec(p(HGNC:IL1B)) View Subject | View Object

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

act(complex(GO:"NLRP1 inflammasome complex")) increases sec(p(HGNC:IL18)) View Subject | View Object

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

path(MESH:"Spinal Cord Injuries") increases act(complex(GO:"NLRP1 inflammasome complex")) View Subject | View Object

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

path(MESH:"Spinal Cord Injuries") increases sec(p(HGNC:IL18)) View Subject | View Object

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

path(MESH:"Spinal Cord Injuries") increases sec(p(HGNC:IL1B)) View Subject | View Object

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

Evidence 4f795740ef
JSON

In support, a recent study in APP/PS1 mice confirms that the NLRP3 inflammasome contributes to the AD pathology (Heneka et al., 2013)

complex(GO:"NLRP3 inflammasome complex") association path(MESH:"Alzheimer Disease") View Subject | View Object

Appears in Networks:
Annotations
Confidence
Medium

path(MESH:"Alzheimer Disease") association complex(GO:"NLRP3 inflammasome complex") View Subject | View Object

Appears in Networks:
Annotations
Confidence
Medium

Evidence 7f773f4516
JSON

Similarly, inhibiting the NLRP3 inflammasome reduces the neuritic plaque burden in an AD transgenic mouse model (Shi et al., 2013)

complex(GO:"NLRP3 inflammasome complex") increases path(MESH:"Plaque, Amyloid") View Subject | View Object

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

Evidence 1c87f5ae9e
JSON

Inflammasomes involve in the maturation of IL-1β and IL-18 are expressed in neurons (de Rivero Vaccari et al., 2008; Yang-Wei Fann et al., 2013; Zou and Crews, 2012)

complex(GO:"inflammasome complex") positiveCorrelation p(HGNC:IL1B) View Subject | View Object

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

complex(GO:"inflammasome complex") positiveCorrelation p(HGNC:IL18) View Subject | View Object

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

p(HGNC:IL18) positiveCorrelation complex(GO:"inflammasome complex") View Subject | View Object

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

p(HGNC:IL1B) positiveCorrelation complex(GO:"inflammasome complex") View Subject | View Object

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

Evidence a3da9e7b27
JSON

IL-1β and IL-18 are synthesized as inactive precursors, proIL-1β and proIL-18, respectively, and require inflammasomes for their maturation

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

Appears in Networks:
Annotations
Confidence
High
NeuroMMSigDB
Interleukin signaling subgraph

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

Appears in Networks:
Annotations
Confidence
High
NeuroMMSigDB
Interleukin signaling subgraph

Evidence 74785089ac
JSON

However the maturation of IL-18 and IL-1β could be regulated by the same type of inflammasome

complex(GO:"inflammasome complex") regulates p(HGNC:IL1B) View Subject | View Object

Appears in Networks:
Annotations
Confidence
High
NeuroMMSigDB
Interleukin signaling subgraph

complex(GO:"inflammasome complex") regulates p(HGNC:IL18) View Subject | View Object

Appears in Networks:
Annotations
Confidence
High
NeuroMMSigDB
Interleukin signaling subgraph

Evidence 77ea524c4f
JSON

Like IL-1β, in most cases, the mature secretable form of IL-18 is generated by caspase-1 through the activation of inflammasome

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

Appears in Networks:
Annotations
Confidence
High
NeuroMMSigDB
Interleukin signaling subgraph

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

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

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

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

Evidence a376473487
JSON

As for the NLRP1 and NLRP3 inflammasomes, the oligomerzied NLRs recruit and interact with the adaptor protein ASC, which in turn recruits the effector protein procaspase-1 that is central to the activation of inflammasomes (Huang et al., 2013)

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

Appears in Networks:
Annotations
Confidence
High
NeuroMMSigDB
Caspase subgraph

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

Appears in Networks:
Annotations
Confidence
High
NeuroMMSigDB
Caspase subgraph

Evidence f50995612e
JSON

Caspase-1 is the protease that cleaves the precursor of the proinflammatory molecules to form their mature form, such as IL-1β and IL-18 (Schroder and Tschopp, 2010)

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

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

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

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

Evidence 9e900dca4e
JSON

For example, down-regulation of NLRP1 in macrophages trigger by Cordyceps sinensis mycelium reduces both IL-18 and IL-1β levels (Huang et al., 2013)

p(HGNC:NLRP1) increases p(HGNC:IL18) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
Confidence
High
NeuroMMSigDB
Interleukin signaling subgraph

p(HGNC:NLRP1) increases p(HGNC:IL1B) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
Confidence
High
NeuroMMSigDB
Interleukin signaling subgraph

Evidence 0a7edad603
JSON

They include the adaptor protein, ASC (apoptosis-associated speck-like protein containing a caspase recruitment domain), which is an essential component of the NLRP1, NLRP2 and NLRP3 inflammasomes, but not of the more complex NLRC4 inflammasome (Martinon et al., 2009; Minkiewicz et al., 2013; Schroder and Tschopp, 2010)

p(HGNC:PYCARD) association composite(complex(GO:"inflammasome complex"), p(HGNC:NLRP2)) View Subject | View Object

Appears in Networks:
Annotations
Confidence
Medium
NeuroMMSigDB
Caspase subgraph

composite(complex(GO:"inflammasome complex"), p(HGNC:NLRP2)) association p(HGNC:PYCARD) View Subject | View Object

Appears in Networks:
Annotations
Confidence
Medium
NeuroMMSigDB
Caspase subgraph

Evidence a7b0f84bed
JSON

Under certain but not all conditions ASC (Martinon et al., 2009) or Naip5 (NLR family, apoptosis inhibitory protein 5) (Lightfield et al., 2011) is required for the activity of the NLRC4 inflammasome

p(HGNC:PYCARD) increases act(complex(GO:"IPAF inflammasome complex")) View Subject | View Object

Appears in Networks:
Annotations
Confidence
High
NeuroMMSigDB
Caspase subgraph

p(HGNC:NAIP) increases act(complex(GO:"IPAF inflammasome complex")) View Subject | View Object

Appears in Networks:
Annotations
Confidence
High
NeuroMMSigDB
Caspase subgraph

Evidence 7a3cf1dc64
JSON

The adaptor protein ASC is important for the activation of NLRC4 inflammasome in astrocytes, while Naip 5 is not (Liu and Chan, 2014)

p(HGNC:PYCARD) increases act(complex(GO:"IPAF inflammasome complex")) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
astrocyte
Confidence
High
NeuroMMSigDB
Caspase subgraph

Evidence 3ddab850ec
JSON

ASC neutralization reduces the upregulation in IL-18 and IL-1β levels (de Rivero Vaccari et al., 2008)

p(HGNC:PYCARD) increases p(HGNC:IL18) View Subject | View Object

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

p(HGNC:PYCARD) increases p(HGNC:IL1B) View Subject | View Object

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

Evidence 83b86d0ac8
JSON

Reducing NLRC4 or ASC levels in the palmitate (PA)-treated astrocytes significantly reduces IL-1β production (Liu and Chan, 2014)

composite(a(CHEBI:hexadecanoate), p(HGNC:NLRC4)) increases p(HGNC:IL1B) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
astrocyte
Confidence
High
NeuroMMSigDB
Caspase subgraph
NeuroMMSigDB
Interleukin signaling subgraph

composite(a(CHEBI:hexadecanoate), p(HGNC:PYCARD)) increases p(HGNC:IL1B) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
astrocyte
Confidence
High
NeuroMMSigDB
Caspase subgraph
NeuroMMSigDB
Interleukin signaling subgraph

Evidence dd34a34bd9
JSON

A subsequent study demonstrated that P2X7 purinergic receptor is involved in the activation of NLRP1 inflammasome (Silverman et al., 2009)

p(HGNC:P2RX7) increases act(complex(GO:"NLRP1 inflammasome complex")) View Subject | View Object

Appears in Networks:
Annotations
Confidence
High

Evidence 650d98247d
JSON

Similarly, the P2X7 purinergic receptor has been shown to activate the NLRP1 inflammasome in primary neurons (Silverman et al., 2009)

p(HGNC:P2RX7) increases act(complex(GO:"NLRP1 inflammasome complex")) View Subject | View Object

Appears in Networks:
Annotations
Confidence
High

Evidence 4ac624cee7
JSON

Deficiency of the NLRP3 gene reduces Aβ deposition and plays a protective role on memory and behavior (Heneka et al.,2013)

g(HGNC:NLRP3) increases a(CHEBI:"amyloid-beta") View Subject | View Object

Appears in Networks:
Annotations
Confidence
High
NeuroMMSigDB
Amyloidogenic subgraph
NeuroMMSigDB
Caspase subgraph

g(HGNC:NLRP3) decreases bp(GO:memory) View Subject | View Object

Appears in Networks:
Annotations
Confidence
High
NeuroMMSigDB
Amyloidogenic subgraph
NeuroMMSigDB
Caspase subgraph

g(HGNC:NLRP3) decreases bp(GO:behavior) View Subject | View Object

Appears in Networks:
Annotations
Confidence
High
NeuroMMSigDB
Amyloidogenic subgraph
NeuroMMSigDB
Caspase subgraph

Evidence 99cc7c1c6c
JSON

Interleukins, in particular IL-1β and IL-18, are upregulated in AD brain, and the overexpression of IL-1β or IL-18 is critical for the onset of the inflammatory process (Rubio-Perez and Morillas-Ruiz, 2012), and both mediate the expression of a vast array of inflammatory genes (Weber et al., 2010)

p(HGNC:IL18) positiveCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

Appears in Networks:
Annotations
Confidence
High
NeuroMMSigDB
Inflammatory response subgraph
NeuroMMSigDB
Interleukin signaling subgraph

p(HGNC:IL18) increases bp(GO:"inflammatory response") View Subject | View Object

Appears in Networks:
Annotations
Confidence
High
NeuroMMSigDB
Inflammatory response subgraph
NeuroMMSigDB
Interleukin signaling subgraph

p(HGNC:IL1B) positiveCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

Appears in Networks:
Annotations
Confidence
High
NeuroMMSigDB
Inflammatory response subgraph
NeuroMMSigDB
Interleukin signaling subgraph

p(HGNC:IL1B) increases bp(GO:"inflammatory response") View Subject | View Object

Appears in Networks:
Annotations
Confidence
High
NeuroMMSigDB
Inflammatory response subgraph
NeuroMMSigDB
Interleukin signaling subgraph

path(MESH:"Alzheimer Disease") positiveCorrelation p(HGNC:IL1B) View Subject | View Object

Appears in Networks:
Annotations
Confidence
High
NeuroMMSigDB
Inflammatory response subgraph
NeuroMMSigDB
Interleukin signaling subgraph

path(MESH:"Alzheimer Disease") positiveCorrelation p(HGNC:IL18) View Subject | View Object

Appears in Networks:
Annotations
Confidence
High
NeuroMMSigDB
Inflammatory response subgraph
NeuroMMSigDB
Interleukin signaling subgraph

Evidence e652580726
JSON

In support, knockout of NLRP3 and caspase-1 have been shown to suppress amyloidogenesis and neuropathology, and improve cognition in AD transgenic mice (Heneka et al., 2013)

p(MGI:Casp1) increases bp(GO:"amyloid-beta formation") View Subject | View Object

Appears in Networks:
Annotations
Confidence
High
MeSH
Alzheimer Disease
NeuroMMSigDB
Amyloidogenic subgraph
NeuroMMSigDB
Caspase subgraph

p(MGI:Casp1) increases a(MESH:Neuropathology) View Subject | View Object

Appears in Networks:
Annotations
Confidence
High
MeSH
Alzheimer Disease
NeuroMMSigDB
Caspase subgraph

p(MGI:Casp1) decreases bp(GO:cognition) View Subject | View Object

Appears in Networks:
Annotations
Confidence
High
MeSH
Alzheimer Disease
NeuroMMSigDB
Caspase subgraph

p(MGI:Nlrp3) increases bp(GO:"amyloid-beta formation") View Subject | View Object

Appears in Networks:
Annotations
Confidence
High
MeSH
Alzheimer Disease
NeuroMMSigDB
Amyloidogenic subgraph
NeuroMMSigDB
Caspase subgraph

p(MGI:Nlrp3) increases a(MESH:Neuropathology) View Subject | View Object

Appears in Networks:
Annotations
Confidence
High
MeSH
Alzheimer Disease
NeuroMMSigDB
Caspase subgraph

p(MGI:Nlrp3) decreases bp(GO:cognition) View Subject | View Object

Appears in Networks:
Annotations
Confidence
High
MeSH
Alzheimer Disease
NeuroMMSigDB
Caspase subgraph

Evidence 86d6a879a7
JSON

A recent report shows that IL-18 and IL-1β are secreted from primed murine dendritic cells in response to Listeria protein p60, but inhibiting NLRP3 reduces the production of IL-1β, but not IL-18 secretion (Schmidt and Lenz, 2012)

p(MGI:Nlrp3) increases p(MGI:Il1b) View Subject | View Object

Appears in Networks:
Annotations
Confidence
High
MeSH
Dendritic Cells
NeuroMMSigDB
Caspase subgraph
NeuroMMSigDB
Interleukin signaling subgraph

Evidence b558ca7e33
JSON

Given that P2X4 and P2X7 are the major purinergic P2X receptor subtypes, a study of spinal cord injury in P2X4 knock-out mice showed a significant reduction in inflammasome activation and proinflammatory cytokine production as compared to wild type (de Rivero Vaccari et al., 2012), supporting the involvement of purinergic receptor P2X4 in the activation of the NLRP1 inflammasome

p(MGI:P2rx4) increases act(complex(GO:"NLRP1 inflammasome complex")) View Subject | View Object

Appears in Networks:
Annotations
Confidence
High

p(MGI:P2rx7) increases act(complex(GO:"NLRP1 inflammasome complex")) View Subject | View Object

Appears in Networks:
Annotations
Confidence
High

Evidence 70a32235f7
JSON

However, upon further study of purinergic receptor P2X4 knockout mice with spinal cord injury, the production of IL-1β but not of IL-18 reduces in the neurons as compared with wild-type mice (de Rivero Vaccari et al., 2012)

p(MGI:P2rx4) increases p(HGNC:IL1B) View Subject | View Object

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

Evidence 4bde981b0f
JSON

P2X4 knock-out mice has been shown to decrease the level of IL-1β and to have impair inflammasome signaling (de Rivero Vaccari et al., 2012)

p(MGI:P2rx4) increases p(HGNC:IL1B) View Subject | View Object

Appears in Networks:
Annotations
Confidence
High
NeuroMMSigDB
Interleukin signaling subgraph

p(MGI:P2rx4) increases act(complex(GO:"inflammasome complex")) View Subject | View Object

Appears in Networks:
Annotations
Confidence
High
NeuroMMSigDB
Interleukin signaling subgraph

Evidence 5e26ae2d5a
JSON

Trauma, a risk factor for AD, increases inflammasome expression in rat neurons (de Rivero Vaccari et al., 2009; de Rivero Vaccari et al., 2008)

path(MESH:"Trauma, Nervous System") increases path(MESH:"Alzheimer Disease") View Subject | View Object

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Neurons

path(MESH:"Trauma, Nervous System") increases complex(GO:"inflammasome complex") View Subject | View Object

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Neurons

Evidence f9fe7c12c8
JSON

Furthermore, postmortem brain tissues from stroke patients show increase protein levels of inflammasomes in primary cortical neurons (Yang- Wei Fann et al., 2013)

path(MESH:Stroke) increases complex(GO:"inflammasome complex") View Subject | View Object

Appears in Networks:
Annotations
Confidence
High
MeSH
Neurons

About

BEL Commons is developed and maintained in an academic capacity by Charles Tapley Hoyt and Daniel Domingo-Fernández at the Fraunhofer SCAI Department of Bioinformatics with support from the IMI project, AETIONOMY. It is built on top of PyBEL, an open source project. Please feel free to contact us here to give us feedback or report any issues. Also, see our Publishing Notes and Data Protection information.

If you find BEL Commons useful in your work, please consider citing: Hoyt, C. T., Domingo-Fernández, D., & Hofmann-Apitius, M. (2018). BEL Commons: an environment for exploration and analysis of networks encoded in Biological Expression Language. Database, 2018(3), 1–11.