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  3. PubMed:27288790

PubMed: 27288790

Title
Upstream regulators and downstream effectors of NF-κB in Alzheimer's disease.
Journal
Journal of the neurological sciences
Volume
366
Issue
None
Pages
127-134
Date
2016-07-15
Authors
Zhang K | Han XH | Qi HX | Hong W | Zhen Z | Ting C | Hu ZM | Chang YN | Han YW | Shi ZM

Evidence 8d30ac6154
JSON

Tetrandrine, is an herb-derived bisbenzylioquinoline alkaloid, may be a potent inhibitor of NF-κB activation and can inhibit the expression of iNOS and COX-2 which are involved in pro-inflammation.

a(CHEBI:"(+)-Tetrandrine") decreases act(p(FPLX:NFkappaB)) View Subject | View Object

Appears in Networks:

a(CHEBI:"(+)-Tetrandrine") decreases p(HGNC:NOS2) View Subject | View Object

Appears in Networks:

a(CHEBI:"(+)-Tetrandrine") decreases p(HGNC:PTGS2) View Subject | View Object

Appears in Networks:

p(HGNC:NOS2) increases path(MESH:Inflammation) View Subject | View Object

Appears in Networks:

p(HGNC:PTGS2) increases path(MESH:Inflammation) View Subject | View Object

Appears in Networks:

Evidence fd5df60511
JSON

Treatment with p38 inhibitor, SB239063, prevents downstream phosphorylation of IκBα and p65 translocation to the nucleus in the ventral midbrain.

a(CHEBI:"SB-239063") decreases act(p(HGNC:MAPK14)) View Subject | View Object

Appears in Networks:

act(p(HGNC:MAPK14)) increases p(HGNC:NFKBIA, pmod(Ph)) View Subject | View Object

Appears in Networks:

act(p(HGNC:MAPK14)) increases tloc(p(HGNC:RELA), fromLoc(MESH:Cytosol), toLoc(MESH:"Cell Nucleus")) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Mesencephalon

Evidence c5ad684352
JSON

AGEs induce tau hyperphosphorylation, memory deterioration, decline of synaptic proteins, and impairment of long-term potentiation in rats [10].

a(CHEBI:"advanced glycation end-product") increases p(HGNC:MAPT, pmod(HBP:hyperphosphorylation)) View Subject | View Object

Appears in Networks:

a(CHEBI:"advanced glycation end-product") decreases bp(GO:memory) View Subject | View Object

Appears in Networks:

a(CHEBI:"advanced glycation end-product") increases bp(GO:"cellular protein catabolic process") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Synapses

a(CHEBI:"advanced glycation end-product") decreases bp(GO:"long-term synaptic potentiation") View Subject | View Object

Appears in Networks:

Evidence 135df9b282
JSON

Results have shown a sig- nificant increase in phosphorylation of IκB at serine 32–36 and NF-κB at serine 536 with Aβ 42 exposure, this phosphorylation enhances p65 transactivation potential [16].

a(CHEBI:"amyloid-beta polypeptide 42") increases p(FPLX:IKB, pmod(Ph, Ser, 32)) View Subject | View Object

Appears in Networks:

a(CHEBI:"amyloid-beta polypeptide 42") increases p(FPLX:IKB, pmod(Ph, Ser, 36)) View Subject | View Object

Appears in Networks:

a(CHEBI:"amyloid-beta polypeptide 42") increases p(FPLX:NFkappaB, pmod(Ph, Ser, 536)) View Subject | View Object

Appears in Networks:

p(FPLX:NFkappaB, pmod(Ph, Ser, 536)) increases act(p(HGNC:RELA)) View Subject | View Object

Appears in Networks:

Evidence 6a4d34a96e
JSON

Aβ 42 mediated increase in BACE1 expression is accompanied by a decrease in Uch-L1 expression and activity in dif- ferent cellular models and in sporadic AD brains, which interferes with the lysosomal degradation of BACE1 [52,56].

a(CHEBI:"amyloid-beta polypeptide 42") increases p(HGNC:BACE1) View Subject | View Object

Appears in Networks:

p(HGNC:UCHL1) decreases p(HGNC:BACE1) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain
MeSH
Alzheimer Disease

act(p(HGNC:UCHL1)) decreases p(HGNC:BACE1) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain
MeSH
Alzheimer Disease

Evidence 6515ce9a52
JSON

Upon exposure to various cell stressors including Aβ 42 , expression of BACE1-AS becomes elevated, increasing BACE1 mRNA stability and generating additional Aβ 42 through a post-transcriptional feed-forward mechanism [74].

a(CHEBI:"amyloid-beta polypeptide 42") increases r(HGNC:"BACE1-AS") View Subject | View Object

Appears in Networks:

r(HGNC:"BACE1-AS") decreases deg(r(HGNC:BACE1)) View Subject | View Object

Appears in Networks:

r(HGNC:"BACE1-AS") increases a(CHEBI:"amyloid-beta polypeptide 42") View Subject | View Object

Appears in Networks:

Evidence 090eb86d8a
JSON

In cell models triggering supraphysiological concentrations of Aβ pep- tides, NF-κB is activated, as well as in both neuronal cells and microglial cells, showing that NF-κB pathway has been linked to Aβ neurotoxicity [14].

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

Appears in Networks:
Annotations
MeSH
Microglia
MeSH
Neurons

Evidence 52eb3d4875
JSON

Further investigations confirm that the activation of p50 and RelA subunit contributes to the apoptotic program in cells exposed to the Aβ [17].

a(CHEBI:"amyloid-beta") increases act(p(HGNC:NFKB1)) View Subject | View Object

Appears in Networks:

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

Appears in Networks:

act(p(HGNC:RELA)) increases bp(GO:"apoptotic process") View Subject | View Object

Appears in Networks:

act(p(HGNC:NFKB1)) increases bp(GO:"apoptotic process") View Subject | View Object

Appears in Networks:

Evidence b092eca372
JSON

In contrast, SP600125 treatment, a JNK inhibitor, increases the p38 MAPK depen- dent phosphorylation of p65 NF-κB subunit in the nucleus [47].

a(CHEBI:"anthra[1,9-cd]pyrazol-6(2H)-one") decreases p(FPLX:JNK) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Cell Nucleus

a(CHEBI:"anthra[1,9-cd]pyrazol-6(2H)-one") increases act(p(HGNC:MAPK14)) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Cell Nucleus

act(p(HGNC:MAPK14)) increases p(HGNC:NFKBIA, pmod(Ph)) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Cell Nucleus

Evidence 05b5dcf5da
JSON

Previous find- ings have identified ROS as a common denominator of NF-κB activating signals, as Chetsawang B found that NF-κB was increased in H 2 O 2 -treat- ed SH-SY5Y cells [22,23].

a(CHEBI:"hydrogen peroxide") increases act(p(FPLX:NFkappaB)) View Subject | View Object

Appears in Networks:
Annotations
Experimental Factor Ontology (EFO)
SH-SY5Y

a(CHEBI:"reactive oxygen species") increases act(p(FPLX:NFkappaB)) View Subject | View Object

Appears in Networks:
Annotations
Experimental Factor Ontology (EFO)
SH-SY5Y

Evidence 1cc7d150d3
JSON

Omega-6 phospholipids, e.g. dilinoleoylphosphatidylcholine (DLPC), have been shown to block TNF-α and H 2 O 2 activation of MAPK as well as blocks IκBα phosphorylation in the SH-SY5Y cells and prevents the phosphorylation and activation of NF-κB.

a(CHEBI:"hydrogen peroxide") increases act(p(FPLX:ERK)) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Cerebral Cortex
MeSH
Hippocampus

a(PUBCHEM:6440944) decreases act(p(FPLX:ERK)) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Cerebral Cortex
MeSH
Hippocampus

a(PUBCHEM:6440944) decreases p(HGNC:NFKBIA, pmod(Ph)) View Subject | View Object

Appears in Networks:
Annotations
Experimental Factor Ontology (EFO)
SH-SY5Y
MeSH
Cerebral Cortex
MeSH
Hippocampus

a(PUBCHEM:6440944) decreases p(FPLX:NFkappaB, pmod(Ph)) View Subject | View Object

Appears in Networks:
Annotations
Experimental Factor Ontology (EFO)
SH-SY5Y
MeSH
Cerebral Cortex
MeSH
Hippocampus

a(PUBCHEM:6440944) decreases act(p(FPLX:NFkappaB)) View Subject | View Object

Appears in Networks:
Annotations
Experimental Factor Ontology (EFO)
SH-SY5Y
MeSH
Cerebral Cortex
MeSH
Hippocampus

p(HGNC:TNF) increases act(p(FPLX:ERK)) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Cerebral Cortex
MeSH
Hippocampus

Evidence 551c0fd197
JSON

What's more, DLPC complete- ly abolishes TNF-α and H 2 O 2 induced neuronal tau phosphorylation, re- duces cellular APP levels and Aβ expression and secretion in SH-SY5Y cells [91,92] (Table 1).

a(CHEBI:"hydrogen peroxide") increases p(HGNC:MAPT, pmod(Ph)) View Subject | View Object

Appears in Networks:
Annotations
Experimental Factor Ontology (EFO)
SH-SY5Y
MeSH
Cerebral Cortex
MeSH
Hippocampus

a(PUBCHEM:6440944) decreases p(HGNC:MAPT, pmod(Ph)) View Subject | View Object

Appears in Networks:
Annotations
Experimental Factor Ontology (EFO)
SH-SY5Y
MeSH
Cerebral Cortex
MeSH
Hippocampus

a(PUBCHEM:6440944) decreases p(HGNC:APP) View Subject | View Object

Appears in Networks:
Annotations
Experimental Factor Ontology (EFO)
SH-SY5Y
MeSH
Cerebral Cortex
MeSH
Hippocampus

a(PUBCHEM:6440944) decreases a(CHEBI:"amyloid-beta") View Subject | View Object

Appears in Networks:
Annotations
Experimental Factor Ontology (EFO)
SH-SY5Y
MeSH
Cerebral Cortex
MeSH
Hippocampus

a(PUBCHEM:6440944) decreases sec(a(CHEBI:"amyloid-beta")) View Subject | View Object

Appears in Networks:
Annotations
Experimental Factor Ontology (EFO)
SH-SY5Y
MeSH
Cerebral Cortex
MeSH
Hippocampus

p(HGNC:TNF) increases p(HGNC:MAPT, pmod(Ph)) View Subject | View Object

Appears in Networks:
Annotations
Experimental Factor Ontology (EFO)
SH-SY5Y
MeSH
Cerebral Cortex
MeSH
Hippocampus

Evidence 3d73ef557d
JSON

Under different envi- ronmental conditions such as Aβ/ROS/cytokines accumulation, the IκB kinase (IKK) complex becomes activated and mediates the phosphoryla- tion of IκBs, then IκBs are degradated and the remaining NF-κB dimer is activated and thus translocates to the nucleus where it binds to the DNA consensus sequence of various target genes [9–11].

a(CHEBI:"reactive oxygen species") increases act(p(FPLX:"IKK_complex")) View Subject | View Object

Appears in Networks:

a(HBP:"amyloid-beta aggregates") increases act(p(FPLX:"IKK_complex")) View Subject | View Object

Appears in Networks:

a(MESH:Cytokines) increases act(p(FPLX:"IKK_complex")) View Subject | View Object

Appears in Networks:

act(p(FPLX:NFkappaB)) increases tloc(p(FPLX:NFkappaB), fromLoc(MESH:Cytosol), toLoc(MESH:"Cell Nucleus")) View Subject | View Object

Appears in Networks:

act(p(FPLX:NFkappaB)) increases complex(a(MESH:DNA), p(FPLX:NFkappaB)) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Cell Nucleus

act(p(FPLX:"IKK_complex")) increases p(FPLX:IKB, pmod(Ph)) View Subject | View Object

Appears in Networks:

deg(p(FPLX:IKB)) increases act(p(FPLX:NFkappaB)) View Subject | View Object

Appears in Networks:

p(FPLX:IKB, pmod(Ph)) increases deg(p(FPLX:IKB)) View Subject | View Object

Appears in Networks:

Evidence fb8f712358
JSON

Higher levels of ROS biomarkers are characteristic of AD patients in clinical and preclinical studies, resulting in the alteration of membrane proper- ties, such as fluidity, ion transport, enzyme activities, protein cross- linking, tau protein hyperphosphorylation, autophagic dysfunction and eventually neuron cell death [20].

a(CHEBI:"reactive oxygen species") positiveCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

Appears in Networks:

a(CHEBI:"reactive oxygen species") association bp(MESH:"Membrane Fluidity") View Subject | View Object

Appears in Networks:

a(CHEBI:"reactive oxygen species") association bp(GO:"ion transport") View Subject | View Object

Appears in Networks:

a(CHEBI:"reactive oxygen species") increases p(HGNC:MAPT, pmod(HBP:hyperphosphorylation)) View Subject | View Object

Appears in Networks:

a(CHEBI:"reactive oxygen species") decreases bp(GO:autophagy) View Subject | View Object

Appears in Networks:

bp(GO:"ion transport") association a(CHEBI:"reactive oxygen species") View Subject | View Object

Appears in Networks:

bp(MESH:"Membrane Fluidity") association a(CHEBI:"reactive oxygen species") View Subject | View Object

Appears in Networks:

path(MESH:"Alzheimer Disease") positiveCorrelation a(CHEBI:"reactive oxygen species") View Subject | View Object

Appears in Networks:

Evidence 88d2355b0b
JSON

ROS has been found not only the regulators of NF-κB, interestingly, iNOS is also regulated by NF-κB.

a(CHEBI:"reactive oxygen species") regulates act(p(FPLX:NFkappaB)) View Subject | View Object

Appears in Networks:

p(FPLX:NFkappaB) regulates act(p(HGNC:NOS2)) View Subject | View Object

Appears in Networks:

Evidence 9726bbee55
JSON

ROS generation leads to phosphorylation of NF-κB cytoplasmic inhibitor IκBα. NF-κB is thus liberated and transports to the nucleus.

a(CHEBI:"reactive oxygen species") increases p(HGNC:NFKBIA, pmod(Ph)) View Subject | View Object

Appears in Networks:

p(HGNC:NFKBIA) decreases act(p(FPLX:NFkappaB)) View Subject | View Object

Appears in Networks:

p(HGNC:NFKBIA, pmod(Ph)) increases tloc(p(FPLX:NFkappaB), fromLoc(MESH:Cytosol), toLoc(MESH:"Cell Nucleus")) View Subject | View Object

Appears in Networks:

Evidence 7b3440adc9
JSON

Hydroxytyrosol is an orally bioavailable polyphenol, obtained from ol- ives, which inhibits NF-κB activity and has elicited promising efficacy signals in several inflammatory diseases [88].

a(CHEBI:hydroxytyrosol) decreases act(p(FPLX:NFkappaB)) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Cerebral Cortex
MeSH
Hippocampus

Evidence 0131d919e3
JSON

Further- more, naproxen and ibuprofen and perhaps other NSAIDs, can block the inflammation-induced BACE1 transcription and Aβ production [52,87].

a(CHEBI:ibuprofen) decreases r(HGNC:BACE1) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Cerebral Cortex
MeSH
Hippocampus

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

Appears in Networks:
Annotations
MeSH
Cerebral Cortex
MeSH
Hippocampus

a(CHEBI:naproxen) decreases r(HGNC:BACE1) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Cerebral Cortex
MeSH
Hippocampus

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

Appears in Networks:
Annotations
MeSH
Cerebral Cortex
MeSH
Hippocampus

Evidence 66ef7688c7
JSON

The antioxidants LY231617, and melatonin pro- tect the neurons against the insult and prevented the Tyr42 phosphorylation of IκBα, which acts to protect the neurons against physiological injury by repressing the insult-induced oxidative stress activation of transcription factor NF-κB [86].

a(CHEBI:melatonin) decreases p(HGNC:NFKBIA, pmod(Ph, Tyr, 42)) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Cerebral Cortex
MeSH
Hippocampus

a(CHEBI:melatonin) decreases act(p(FPLX:NFkappaB)) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Cerebral Cortex
MeSH
Hippocampus

a(PUBCHEM:3968) decreases p(HGNC:NFKBIA, pmod(Ph, Tyr, 42)) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Cerebral Cortex
MeSH
Hippocampus

a(PUBCHEM:3968) decreases act(p(FPLX:NFkappaB)) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Cerebral Cortex
MeSH
Hippocampus

Evidence 48ff13a59d
JSON

Nicorandil, ATP-sensitive potassium channel opener, reduced apo- ptosis and decreased oxidative stress, downregulated APP695 mRNA and APP695 protein expression, also reduced Aβ 42 levels in the medium [90].

a(CHEBI:nicorandil) decreases bp(GO:"apoptotic process") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Cerebral Cortex
MeSH
Hippocampus

a(CHEBI:nicorandil) decreases path(MESH:"Oxidative Stress") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Cerebral Cortex
MeSH
Hippocampus

a(CHEBI:nicorandil) decreases p(HBP:APP695) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Cerebral Cortex
MeSH
Hippocampus

a(CHEBI:nicorandil) decreases a(CHEBI:"amyloid-beta polypeptide 42") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Cerebral Cortex
MeSH
Hippocampus

Evidence 8b474abc5f
JSON

Two AGEs, such as pentosidine and glyceraldehyde derived pyridinium (GLAP), both found increased in AD brains, were able to upregulate BACE1 through their binding with RAGE and consequent activation of NF-κB, providing a pathologic link between diabetes and AD [49].

a(CHEBI:pentosidine) positiveCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain

a(HBP:GLAP) positiveCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain

complex(a(CHEBI:pentosidine), p(HGNC:AGER)) increases p(HGNC:BACE1) View Subject | View Object

Appears in Networks:

complex(a(CHEBI:pentosidine), p(HGNC:AGER)) increases act(p(FPLX:NFkappaB)) View Subject | View Object

Appears in Networks:

complex(a(HBP:GLAP), p(HGNC:AGER)) increases p(HGNC:BACE1) View Subject | View Object

Appears in Networks:

complex(a(HBP:GLAP), p(HGNC:AGER)) increases act(p(FPLX:NFkappaB)) View Subject | View Object

Appears in Networks:

path(MESH:"Alzheimer Disease") positiveCorrelation a(CHEBI:pentosidine) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain

path(MESH:"Alzheimer Disease") positiveCorrelation a(HBP:GLAP) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain

Evidence 998c7bfc0f
JSON

In addition, COX-2, mainly regulated by NF-κB, is notably upregulated in the brains of AD patients, which may be associated with the formation of Aβ plaque [65].

a(HBP:"amyloid-beta aggregates") association p(HGNC:PTGS2) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain

p(FPLX:NFkappaB) regulates p(HGNC:PTGS2) View Subject | View Object

Appears in Networks:

p(HGNC:PTGS2) positiveCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain

p(HGNC:PTGS2) association a(HBP:"amyloid-beta aggregates") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain

path(MESH:"Alzheimer Disease") positiveCorrelation p(HGNC:PTGS2) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain

Evidence 4ce1f53b9e
JSON

NSAIDs inhibit BACE1 tran- scriptional activation induced by strong NF-κB activator TNF-α.

a(MESH:"Anti-Inflammatory Agents, Non-Steroidal") decreases act(p(HGNC:BACE1)) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Cerebral Cortex
MeSH
Hippocampus

p(HGNC:TNF) increases act(p(FPLX:NFkappaB)) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Cerebral Cortex
MeSH
Hippocampus

p(HGNC:TNF) increases act(p(HGNC:BACE1)) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Cerebral Cortex
MeSH
Hippocampus

Evidence 3a85d99c97
JSON

Moreover, miRNA-155 is strongly and rapidly up-regulated by inflammatory cytokines and also is an inducible miRNA under transcriptional control by NF-κB.

a(MESH:Cytokines) increases m(MIRBASE:"hsa-mir-155") View Subject | View Object

Appears in Networks:

act(p(FPLX:NFkappaB), ma(tscript)) increases m(MIRBASE:"hsa-mir-155") View Subject | View Object

Appears in Networks:

Evidence b4eab1808c
JSON

LPS treatment induced the nuclear translocation of NF-κB and increased the expression and secretion of TNF-α and IL-1β [63].

a(MESH:Lipopolysaccharides) increases tloc(p(FPLX:NFkappaB), fromLoc(MESH:Cytosol), toLoc(MESH:"Cell Nucleus")) View Subject | View Object

Appears in Networks:

a(MESH:Lipopolysaccharides) increases p(HGNC:TNF) View Subject | View Object

Appears in Networks:

a(MESH:Lipopolysaccharides) increases sec(p(HGNC:TNF)) View Subject | View Object

Appears in Networks:

a(MESH:Lipopolysaccharides) increases p(HGNC:IL1B) View Subject | View Object

Appears in Networks:

a(MESH:Lipopolysaccharides) increases sec(p(HGNC:IL1B)) View Subject | View Object

Appears in Networks:

Evidence 5908244a1e
JSON

The activity of NF-κB in the cell models was strongly inhibited by morphine, which was achieved by a marked up-regulation of the inhibitor of IκB.

a(MESH:Morphine) increases p(FPLX:IKB) View Subject | View Object

Appears in Networks:

a(MESH:Morphine) decreases act(p(FPLX:NFkappaB)) View Subject | View Object

Appears in Networks:

Evidence 37690a6225
JSON

L-Theanine, an amino acid in green tea, reduced Aβ 42 levels in the cortex and hippocampus of the brain, which is mediated by suppres- sion of ERK/p38 and NF-κB as well as the reduction of macromolecular oxidative damage [81].

a(PUBCHEM:439378) decreases a(CHEBI:"amyloid-beta polypeptide 42") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Cerebral Cortex
MeSH
Hippocampus

a(PUBCHEM:439378) decreases p(FPLX:ERK) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Cerebral Cortex
MeSH
Hippocampus

a(PUBCHEM:439378) decreases p(HGNC:MAPK14) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Cerebral Cortex
MeSH
Hippocampus

a(PUBCHEM:439378) decreases p(FPLX:NFkappaB) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Cerebral Cortex
MeSH
Hippocampus

Evidence 7c5d83a805
JSON

Evidence has shown that NF-κB can be activated by ERK pathway [44].

bp(GO:"ERK1 and ERK2 cascade") increases act(p(FPLX:NFkappaB)) View Subject | View Object

Appears in Networks:

Evidence 85d55b40bd
JSON

Reports have indicated that MAPK signaling pathways are excessively activated in AD.

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

Appears in Networks:

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

Appears in Networks:

Evidence 86e5c83b9f
JSON

Then the stimulation of RAGE is able to activate the mitogen-activated protein kinase signaling cascades which converge in IκB kinase complex to phosphorylate IκB, thereby release and activate NF-κB, thus trigger NF-κB dependent gene transcription including IL-1β and TNF-α, which in turn induce the translocation of NF-κB to the nucleus [50].

bp(GO:"MAPK cascade") increases p(FPLX:IKB, pmod(Ph)) View Subject | View Object

Appears in Networks:

act(p(HGNC:AGER)) increases bp(GO:"MAPK cascade") View Subject | View Object

Appears in Networks:

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

Appears in Networks:

act(p(FPLX:NFkappaB)) increases p(HGNC:TNF) View Subject | View Object

Appears in Networks:

p(FPLX:IKB, pmod(Ph)) increases act(p(FPLX:NFkappaB)) View Subject | View Object

Appears in Networks:

p(HGNC:IL1B) increases tloc(p(FPLX:NFkappaB), fromLoc(MESH:Cytosol), toLoc(MESH:"Cell Nucleus")) View Subject | View Object

Appears in Networks:

p(HGNC:TNF) increases tloc(p(FPLX:NFkappaB), fromLoc(MESH:Cytosol), toLoc(MESH:"Cell Nucleus")) View Subject | View Object

Appears in Networks:

Evidence b0ad9c86cb
JSON

In the nervous system, NF-κB has been proposed to serve important function by acting as a transcription regulator: it has roles in inflammation, neuronal survival, differentiation, apoptosis, neurite outgrowth, and synaptic plasticity [5], which are impaired in the progression of various neurodegenerative diseases especially in AD.

bp(GO:"apoptotic process") association p(FPLX:NFkappaB) View Subject | View Object

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Annotations
MeSH
Nervous System

bp(GO:"negative regulation of neuron apoptotic process") association p(FPLX:NFkappaB) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Nervous System

bp(GO:"neuron differentiation") association p(FPLX:NFkappaB) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Nervous System

bp(GO:"regulation of synaptic plasticity") association p(FPLX:NFkappaB) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Nervous System

bp(GO:"regulation of synaptic plasticity") negativeCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Nervous System

bp(MESH:"Neuronal Outgrowth") association p(FPLX:NFkappaB) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Nervous System

p(FPLX:NFkappaB) association path(MESH:Inflammation) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Nervous System

p(FPLX:NFkappaB) association bp(GO:"negative regulation of neuron apoptotic process") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Nervous System

p(FPLX:NFkappaB) association bp(GO:"neuron differentiation") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Nervous System

p(FPLX:NFkappaB) association bp(GO:"apoptotic process") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Nervous System

p(FPLX:NFkappaB) association bp(MESH:"Neuronal Outgrowth") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Nervous System

p(FPLX:NFkappaB) association bp(GO:"regulation of synaptic plasticity") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Nervous System

path(MESH:"Alzheimer Disease") negativeCorrelation bp(GO:"regulation of synaptic plasticity") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Nervous System

path(MESH:Inflammation) association p(FPLX:NFkappaB) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Nervous System

Evidence 76861b7746
JSON

Elevated miRNA-146a in AD brain has been shown to also specifically target the interleukin-1 associated ki- nase-1 (IRAK-1) mRNAs, it is believed to contribute to altered innate immune responses and neuroinflammation in degenerating human brain cells and tissues in inflammatory neurodegenerative diseases including AD and in primary human brain cells stressed with ROS- generating metal sulfates [69].

bp(GO:"immune response") association m(MIRBASE:"hsa-mir-146a") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain
MeSH
Neurodegenerative Diseases

m(MIRBASE:"hsa-mir-146a") positiveCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain

m(MIRBASE:"hsa-mir-146a") association r(HGNC:IRAK1) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain
MeSH
Neurodegenerative Diseases

m(MIRBASE:"hsa-mir-146a") association bp(GO:"immune response") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain
MeSH
Neurodegenerative Diseases

m(MIRBASE:"hsa-mir-146a") increases path(HP:Neurodegeneration) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain
MeSH
Neurodegenerative Diseases

path(MESH:"Alzheimer Disease") positiveCorrelation m(MIRBASE:"hsa-mir-146a") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain

r(HGNC:IRAK1) association m(MIRBASE:"hsa-mir-146a") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain
MeSH
Neurodegenerative Diseases

Evidence 840ce08399
JSON

NF-κB is a ubiquitous transcriptional factor, which can be activated by AKT pathway.

bp(GO:"protein kinase B signaling") increases act(p(FPLX:NFkappaB)) View Subject | View Object

Appears in Networks:

Evidence f3a98cd304
JSON

NF-κB activation has also been detected in the brains of AD pa- tients.

act(p(FPLX:NFkappaB)) positiveCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain

path(MESH:"Alzheimer Disease") positiveCorrelation act(p(FPLX:NFkappaB)) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain

Evidence 5bbf51903e
JSON

The decrease in Uch-L1 depends on NF-κB pathway since NF-κB p65 can interact with the −300 bp and −109 bp NF-κB binding sequences of the Uch-L1 gene promoter [55].

act(p(FPLX:NFkappaB)) decreases p(HGNC:UCHL1) View Subject | View Object

Appears in Networks:

Evidence 334e10a175
JSON

Inflammation is a key pathological hall mark of AD [61,62], NF-κB is considered as a primary regulator of inflammatory processes [10].

p(FPLX:NFkappaB) regulates bp(GO:"inflammatory response") View Subject | View Object

Appears in Networks:

path(MESH:"Alzheimer Disease") positiveCorrelation path(MESH:Inflammation) View Subject | View Object

Appears in Networks:

path(MESH:Inflammation) positiveCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

Appears in Networks:

Evidence 7f658be447
JSON

Inhibition of NF-κB leads to decreased induction of cytokines and chemokines by IL-1β and TNF-α.

act(p(FPLX:NFkappaB)) increases a(MESH:Cytokines) View Subject | View Object

Appears in Networks:

act(p(FPLX:NFkappaB)) increases a(MESH:Chemokines) View Subject | View Object

Appears in Networks:

p(HGNC:IL1B) increases a(MESH:Cytokines) View Subject | View Object

Appears in Networks:

p(HGNC:IL1B) increases a(MESH:Chemokines) View Subject | View Object

Appears in Networks:

p(HGNC:TNF) increases a(MESH:Cytokines) View Subject | View Object

Appears in Networks:

p(HGNC:TNF) increases a(MESH:Chemokines) View Subject | View Object

Appears in Networks:

Evidence 5836ef820e
JSON

Inducible miRNAs and lncRNA perform critical regulatory roles in CNS development, several brain-enriched miRNAs are consistently up- regulated by NF-κB, including miRNA-125b [66], miRNA-146a [67] and miRNA-155 [68].

p(FPLX:NFkappaB) increases m(MIRBASE:"hsa-mir-125b-1") View Subject | View Object

Appears in Networks:

p(FPLX:NFkappaB) increases m(MIRBASE:"hsa-mir-125b-2") View Subject | View Object

Appears in Networks:

p(FPLX:NFkappaB) increases m(MIRBASE:"hsa-mir-146a") View Subject | View Object

Appears in Networks:

p(FPLX:NFkappaB) increases m(MIRBASE:"hsa-mir-155") View Subject | View Object

Appears in Networks:

Evidence d863e0c593
JSON

Disruption of NF-κB p65 expression in RelA-KO cells abolished GSK3β's effect on the transcriptional activation of the human BACE1 gene promoter.

composite(p(HGNC:GSK3B), p(HGNC:RELA)) increases r(HGNC:BACE1) View Subject | View Object

Appears in Networks:

Evidence e70691123c
JSON

Stimulation of GSK3β but not GSK3α promoted BACE1 gene expression and BACE1-mediated APP processing in vitro by regulating BACE1 gene promoter activity, which was dependent on NF-κB p65-binding elements in the BACE1 pro- moter [51].

p(HGNC:GSK3B) increases p(HGNC:BACE1) View Subject | View Object

Appears in Networks:

p(HGNC:GSK3A) causesNoChange p(HGNC:BACE1) View Subject | View Object

Appears in Networks:

Evidence 21cc3829f3
JSON

Activation of AKT augments the transactivating activity and produces higher nuclear levels of p65-NF- κB, which is important for neuroprotection.

p(HGNC:RELA) decreases bp(GO:"neuron apoptotic process") View Subject | View Object

Appears in Networks:

act(p(FPLX:AKT)) increases p(HGNC:RELA) View Subject | View Object

Appears in Networks:

Evidence fbc24a8c60
JSON

Pathogenic effects appear to be mediated via specific interaction of miRNA-125b with the 3′-UTR region of mRNA of 15-lipoxygenase (15-LOX) and the vitamin D3 receptor (VDR; VD3R), the downregula- tion of 15-LOX and VDR may therefore be explained by the actions of a single inducible, pro-inflammatory miRNA-125b in hippocampal CA1 of AD brain [71].

m(MIRBASE:"hsa-mir-125b-1") decreases p(HGNC:ALOX15) View Subject | View Object

Appears in Networks:
Annotations
MeSH
CA1 Region, Hippocampal
MeSH
Alzheimer Disease

m(MIRBASE:"hsa-mir-125b-1") decreases p(HGNC:VDR) View Subject | View Object

Appears in Networks:
Annotations
MeSH
CA1 Region, Hippocampal
MeSH
Alzheimer Disease

m(MIRBASE:"hsa-mir-125b-2") decreases p(HGNC:ALOX15) View Subject | View Object

Appears in Networks:
Annotations
MeSH
CA1 Region, Hippocampal
MeSH
Alzheimer Disease

m(MIRBASE:"hsa-mir-125b-2") decreases p(HGNC:VDR) View Subject | View Object

Appears in Networks:
Annotations
MeSH
CA1 Region, Hippocampal
MeSH
Alzheimer Disease

Evidence 88efc41bba
JSON

Specific up-regulation of miRNA-155 is observed in related immunopatho- logic conditions including MS and AD [70].

m(MIRBASE:"hsa-mir-155") positiveCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

Appears in Networks:

m(MIRBASE:"hsa-mir-155") positiveCorrelation path(MESH:"Multiple Sclerosis") View Subject | View Object

Appears in Networks:

path(MESH:"Alzheimer Disease") positiveCorrelation m(MIRBASE:"hsa-mir-155") View Subject | View Object

Appears in Networks:

path(MESH:"Multiple Sclerosis") positiveCorrelation m(MIRBASE:"hsa-mir-155") View Subject | View Object

Appears in Networks:

Evidence 5c33387a4f
JSON

Pharmacologic inhibition of ERK and p38 MAPK and dominant- negative mutation of both enzymes suppressed Aβ-induced NF-κB transactivation thus neurotoxicity by Aβ [45,46].

p(FPLX:ERK) increases act(p(FPLX:NFkappaB)) View Subject | View Object

Appears in Networks:

p(HGNC:MAPK14) increases act(p(FPLX:NFkappaB)) View Subject | View Object

Appears in Networks:

Evidence dfcc879cbd
JSON

TNF-α [27], IL-1β [28], IL-18 [29], CXCL10 [30] and TGF-β1 [31] are known to be elevated in the AD brain.

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

Appears in Networks:
Annotations
MeSH
Brain

p(HGNC:CXCL10) positiveCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain

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

Appears in Networks:
Annotations
MeSH
Brain

p(HGNC:TGFB1) positiveCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain

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

Appears in Networks:
Annotations
MeSH
Brain

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

Appears in Networks:
Annotations
MeSH
Brain

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

Appears in Networks:
Annotations
MeSH
Brain

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

Appears in Networks:
Annotations
MeSH
Brain

path(MESH:"Alzheimer Disease") positiveCorrelation p(HGNC:CXCL10) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain

path(MESH:"Alzheimer Disease") positiveCorrelation p(HGNC:TGFB1) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain

Evidence 7c699c1089
JSON

Cortical neurons stimulated with IL-18 also generated NF-κB activation [33].

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

Appears in Networks:
Annotations
Cell Ontology (CL)
cerebral cortex neuron

Evidence b579a01681
JSON

Nuclear local- ization of NF-κB in differentiated neuron progenitor cells (NPCs) is in- creasing following exposure to IL-1β and TNF-α, strong inducers of the NF-κB pathway with increase in the phosphorylation of IKK and p65 while decrease in the level of IκB [32].

p(HGNC:IL1B) increases tloc(p(FPLX:NFkappaB), fromLoc(MESH:Cytosol), toLoc(MESH:"Cell Nucleus")) View Subject | View Object

Appears in Networks:

p(HGNC:IL1B) increases p(FPLX:"IKK_complex", pmod(Ph)) View Subject | View Object

Appears in Networks:

p(HGNC:IL1B) increases p(HGNC:RELA, pmod(Ph)) View Subject | View Object

Appears in Networks:

p(HGNC:IL1B) decreases p(FPLX:IKB) View Subject | View Object

Appears in Networks:

p(HGNC:TNF) increases tloc(p(FPLX:NFkappaB), fromLoc(MESH:Cytosol), toLoc(MESH:"Cell Nucleus")) View Subject | View Object

Appears in Networks:

p(HGNC:TNF) increases p(FPLX:"IKK_complex", pmod(Ph)) View Subject | View Object

Appears in Networks:

p(HGNC:TNF) increases p(HGNC:RELA, pmod(Ph)) View Subject | View Object

Appears in Networks:

p(HGNC:TNF) decreases p(FPLX:IKB) View Subject | View Object

Appears in Networks:

Evidence b6a73bfdb3
JSON

BACE1-AS regulates BACE1 mRNA and subsequently BACE1 protein expression in vitro and in vivo.

r(HGNC:"BACE1-AS") regulates r(HGNC:BACE1) View Subject | View Object

Appears in Networks:

r(HGNC:"BACE1-AS") regulates p(HGNC:BACE1) View Subject | View Object

Appears in Networks:

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.