General Information:

Id: 3,761
Diseases: Alzheimer disease - [OMIM]
Mammalia
review
Reference: Azizi G and Mirshafiey A(2012) The potential role of proinflammatory and antiinflammatory cytokines in Alzheimer disease pathogenesis Immunopharmacol Immunotoxicol 34: 881-895 [PMID: 22970774]

Interaction Information:

Comment Antiinflammatory cytokines are IL-4, IL-10 and IL-13. They can activate M2 subtype.
Formal Description
Interaction-ID: 36609

gene/protein

IL4

increases_activity of

Comment Antiinflammatory cytokines are IL-4, IL-10 and IL-13. They can activate M2 subtype.
Formal Description
Interaction-ID: 36638

gene/protein

IL10

increases_activity of

Comment Antiinflammatory cytokines are IL-4, IL-10 and IL-13. They can activate M2 subtype.
Formal Description
Interaction-ID: 36639

gene/protein

IL13

increases_activity of

Comment Antiinflammatory cytokines are IL-4, IL-10 and IL-13. They can activate M2 subtype.
Formal Description
Interaction-ID: 36640

gene/protein

IL4

increases_activity of

tissue/cell line

M2 macrophage

Comment Antiinflammatory cytokines are IL-4, IL-10 and IL-13. They can activate M2 subtype.
Formal Description
Interaction-ID: 36641

gene/protein

IL10

increases_activity of

tissue/cell line

M2 macrophage

Comment Antiinflammatory cytokines are IL-4, IL-10 and IL-13. They can activate M2 subtype.
Formal Description
Interaction-ID: 36642

gene/protein

IL13

increases_activity of

tissue/cell line

M2 macrophage

Comment M1 phenotype produces proinflammatory cytokines such as TNF and IL-12 p70.
Formal Description
Interaction-ID: 36705

tissue/cell line

M1 macrophage

increases_quantity of

gene/protein

TNF

Drugbank entries Show/Hide entries for TNF
Comment M1 phenotype produces proinflammatory cytokines such as TNF and IL-12 p70.
Formal Description
Interaction-ID: 36707

tissue/cell line

M1 macrophage

increases_quantity of

gene/protein

IL-12 p70

Comment M2 phenotypes typically produce IL-10, IL-1Ra, and IL-1 decoy receptor type II.
Formal Description
Interaction-ID: 36708

tissue/cell line

M2 macrophage

increases_quantity of

gene/protein

IL10

Comment M2 phenotypes typically produce IL-10, IL-1Ra, and IL-1 decoy receptor type II.
Formal Description
Interaction-ID: 36709

tissue/cell line

M2 macrophage

increases_quantity of

gene/protein

IL1RN

Comment M2 phenotypes typically produce IL-10, IL-1Ra, and IL-1 decoy receptor type II.
Formal Description
Interaction-ID: 36710

tissue/cell line

M2 macrophage

increases_quantity of

gene/protein

IL1R2

Comment Microglia interact with fAbeta through an ensemble of surface receptors composed of the alpha(6)beta(1) integrin, CD36, CD47, and the class A scavenger receptor.
Formal Description
Interaction-ID: 36713

tissue/cell line

microglia

interacts (colocalizes) with

complex/PPI

Amyloid beta peptide (fibrillar)

through an ensemble of surface receptors composed of the alpha(6)beta(1) integrin, CD36, CD47, and the class A scavenger receptor
Comment fAbeta binds to CD36 a type B scavenger receptor, and initiate a signaling cascade that regulates microglial recruitment, activation, and secretion of inflammatory mediators leading to neuronal dysfunction and death.
Formal Description
Interaction-ID: 36714

complex/PPI

Amyloid beta peptide (fibrillar)

interacts (colocalizes) with

gene/protein

CD36

Comment fAbeta binds to CD36 a type B scavenger receptor, and initiate a signaling cascade that regulates microglial recruitment, activation, and secretion of inflammatory mediators leading to neuronal dysfunction and death.
Formal Description
Interaction-ID: 36715

complex/PPI

Amyloid beta peptide (fibrillar)

increases_activity of

that regulates microglial recruitment, activation, and secretion of inflammatory mediators
Comment RAGE (Receptor for Advanced Glycation Endproducts) is a multiligand member of the Ig superfamily of cell surface molecules which serves as a receptor for Abeta on neurons, microglia, astrocytes, and cells of vessel wall.
Formal Description
Interaction-ID: 36752

gene/protein

AGER

interacts (colocalizes) with

gene/protein

Amyloid beta peptide

on neurons, microglia, astrocytes, and cells of vessel wall
Comment Advanced glycation endproducts (AGEs) accumulate on protein deposits including the beta-amyloid plaques in AD.
Formal Description
Interaction-ID: 36753

drug/chemical compound

Advanced glycation end-product

interacts (colocalizes) with

in Alzheimer disease
Comment Increased expression of RAGE is observed in regions of the brain affected by AD.
Formal Description
Interaction-ID: 36754

increases_quantity of

gene/protein

AGER

in regions of the brain affected by AD
Comment Abeta-RAGE interaction leads to cell stress and transmits its signal using intracellular reactive oxygen species as second messengers.
Formal Description
Interaction-ID: 36755

complex/PPI

AGER-Abeta interaction

increases_activity of

Comment AGEs induce the expression of a variety of proinflammatory markers including the TNF-alpha, MMPs and inducible nitric oxide (NO) synthase.
Formal Description
Interaction-ID: 36756

drug/chemical compound

Advanced glycation end-product

increases_expression of

gene/protein

TNF

Drugbank entries Show/Hide entries for TNF
Comment AGEs induce the expression of a variety of proinflammatory markers including the TNF-alpha, MMPs and inducible nitric oxide (NO) synthase.
Formal Description
Interaction-ID: 36757

drug/chemical compound

Advanced glycation end-product

increases_expression of

gene/protein

Matrix metallopeptidase

Comment AGEs induce the expression of a variety of proinflammatory markers including the TNF-alpha, MMPs and inducible nitric oxide (NO) synthase.
Formal Description
Interaction-ID: 36758

drug/chemical compound

Advanced glycation end-product

increases_expression of

gene/protein

NOS2

Drugbank entries Show/Hide entries for NOS2
Comment AGEs induces Abeta accumulation, impaired learning/memory, and neurotoxicity in an Abeta-rich environment.
Formal Description
Interaction-ID: 36759

drug/chemical compound

Advanced glycation end-product

increases_quantity of

Comment AGEs induces Abeta accumulation, impaired learning/memory, and neurotoxicity in an Abeta-rich environment.
Formal Description
Interaction-ID: 36761

drug/chemical compound

Advanced glycation end-product

decreases_activity of

Comment AGEs induces Abeta accumulation, impaired learning/memory, and neurotoxicity in an Abeta-rich environment.
Formal Description
Interaction-ID: 36762

drug/chemical compound

Advanced glycation end-product

increases_activity of

process

neuron death

in an Abeta-rich environment; via neurotoxicity.
Comment AD is associated with upregulation of proinflammatory cytokines.
Formal Description
Interaction-ID: 36763

increases_quantity of

gene/protein

Proinflammatory cytokine

Comment AD-derived peripheral blood mononuclear cell (PBMC) activated by rAbeta42 induces the production of the proinflammatory cytokines and chemokines.
Formal Description
Interaction-ID: 36767

increases_quantity of

gene/protein

Proinflammatory cytokine

if activated by rAbeta42
Comment AD-derived peripheral blood mononuclear cell (PBMC) activated by rAbeta42 induces the production of the proinflammatory cytokines and chemokines.
Formal Description
Interaction-ID: 36775

increases_quantity of

gene/protein

Chemokine

if activated by rAbeta42
Comment IL-1 is a potent proinflammatory cytokine can contribute to pathophysiology of AD by promoting deposition of Abeta in the brain.
Formal Description
Interaction-ID: 36776

gene/protein

IL1B

affects_activity of

gene/protein

Proinflammatory cytokine

Drugbank entries Show/Hide entries for IL1B
Comment IL-1 is a potent proinflammatory cytokine can contribute to pathophysiology of AD by promoting deposition of Abeta in the brain.
Formal Description
Interaction-ID: 36777

gene/protein

IL1B

affects_activity of

Drugbank entries Show/Hide entries for IL1B
Comment IL-1 is a potent proinflammatory cytokine can contribute to pathophysiology of AD by promoting deposition of Abeta in the brain.
Formal Description
Interaction-ID: 36778

gene/protein

IL1B

affects_quantity of

gene/protein

Amyloid beta peptide

in brain; by promoting deposition of Abeta
Drugbank entries Show/Hide entries for IL1B
Comment IL-1 elevation is a critical component of the brain's response to insults, termed neuroinflammation, and of leukocyte recruitment to the CNS.
Formal Description
Interaction-ID: 36780

gene/protein

IL1B

affects_activity of

phenotype

neuroinflammation

Drugbank entries Show/Hide entries for IL1B
Comment IL-1 elevation is a critical component of the brain's response to insults, termed neuroinflammation, and of leukocyte recruitment to the CNS.
Formal Description
Interaction-ID: 36781

gene/protein

IL1B

affects_activity of

(leukocyte recruitment to the CNS)
Drugbank entries Show/Hide entries for IL1B
Comment IL-1 elevation is a critical component of the brain's response to insults, termed neuroinflammation, and of leukocyte recruitment to the CNS, characterized by astrocytic and microglial activation.
Formal Description
Interaction-ID: 36782

affects_activity of

Comment IL-1 elevation is a critical component of the brain's response to insults, termed neuroinflammation, and of leukocyte recruitment to the CNS, characterized by astrocytic and microglial activation.
Formal Description
Interaction-ID: 36783

affects_activity of

Comment AGER/RAGE is part of RAGE-Abeta interaction.
Formal Description
Interaction-ID: 36784

gene/protein

AGER

is_part_of

complex/PPI

AGER-Abeta interaction

Comment IL-1beta is a potent stimulus for inducible nitric oxide synthase expression and activity in the brain and the spillover of NO metabolites into cerebrospinal fluid.
Formal Description
Interaction-ID: 36785

gene/protein

IL1B

increases_expression of

gene/protein

NOS2

in brain
Drugbank entries Show/Hide entries for IL1B or NOS2
Comment IL-1beta is a potent stimulus for inducible nitric oxide synthase expression and activity in the brain and the spillover of NO metabolites into cerebrospinal fluid.
Formal Description
Interaction-ID: 36786

gene/protein

IL1B

affects transport of

drug/chemical compound

nitric oxide metabolite

into cerebrospinal fluid
Drugbank entries Show/Hide entries for IL1B
Comment QUIN (quinolinic acid, a excitotoxin and neuroactive product of the kynurenine pathway) is an important factor for astroglial activation, dysregulation and cell death with potential relevance to AD and other neuroinflammatory diseases.
Formal Description
Interaction-ID: 36787

drug/chemical compound

Quinolinic acid

affects_activity of

Drugbank entries Show/Hide entries for Quinolinic acid
Comment QUIN (quinolinic acid, a excitotoxin and neuroactive product of the kynurenine pathway) is an important factor for astroglial activation, dysregulation and cell death with potential relevance to AD and other neuroinflammatory diseases.
Formal Description
Interaction-ID: 36788

drug/chemical compound

Quinolinic acid

affects_activity of

process

neuron death

Drugbank entries Show/Hide entries for Quinolinic acid
Comment In human astrocytes, QUIN induces IL-1beta expression and inflammatory mechanisms represented by elevated IL-1beta in patients with MCI, specifically in those with impairment in multiple cognitive domains.
Formal Description
Interaction-ID: 36789

drug/chemical compound

Quinolinic acid

increases_expression of

gene/protein

IL1B

in human astrocytes; in patients with MCI, specifically in those with impairment in multiple cognitive domains
Drugbank entries Show/Hide entries for Quinolinic acid or IL1B
Comment In human astrocytes, QUIN induces IL-1beta expression and inflammatory mechanisms represented by elevated IL-1beta in patients with MCI, specifically in those with impairment in multiple cognitive domains.
Formal Description
Interaction-ID: 36790

drug/chemical compound

Quinolinic acid

affects_activity of

in human astrocytes; in patients with MCI, specifically in those with impairment in multiple cognitive domains
Drugbank entries Show/Hide entries for Quinolinic acid
Comment S100B is an astrocyte-derived cytokine implicated in the IL-1beta-triggered cytokine cycle in AD.
Formal Description
Interaction-ID: 36831

gene/protein

S100B

affects_activity of

gene/protein

Cytokine

implicated in the IL-1beta-triggered cytokine cycle in AD
Drugbank entries Show/Hide entries for S100B
Comment Elevated levels of IL-1beta can induce secretion of the S100B by activated astrocytes as a component of the neuroinflammatory response, which would support the involvement of S100B in the genesis of neurodegenerative diseases.
Formal Description
Interaction-ID: 36832

gene/protein

IL1B

affects_quantity of

gene/protein

S100B

if level of IL-1beta is elevated secretion of the S100B can be induced by activated astrocytes
Drugbank entries Show/Hide entries for IL1B or S100B
Comment Elevated levels of IL-1beta can induce secretion of the S100B by activated astrocytes as a component of the neuroinflammatory response, which would support the involvement of S100B in the genesis of neurodegenerative diseases.
Formal Description
Interaction-ID: 36833

increases_quantity of

gene/protein

S100B

Drugbank entries Show/Hide entries for S100B
Comment Increased risk of AD has been associated with polymorphisms in the IL-1 gene cluster, and in particular with the IL-1alpha-889 T/T genotype, in its 5-end regulatory region (rs1800587) with possible functional effects.
Formal Description
Interaction-ID: 36834

increases_activity of

Comment The interleukin-1 receptor antagonist (IL-1Ra) a physiological antagonist for the IL-1 Receptor is the principal determinant of IL-1beta bioactivity within the IL-1 gene cluster, regulating IL-1alpha and IL-1beta release.
Formal Description
Interaction-ID: 36835

gene/protein

IL1RN

affects_activity of

gene/protein

IL1B

Drugbank entries Show/Hide entries for IL1B
Comment The interleukin-1 receptor antagonist (IL-1Ra) a physiological antagonist for the IL-1 Receptor is the principal determinant of IL-1beta bioactivity within the IL-1 gene cluster, regulating IL-1alpha and IL-1beta release.
Formal Description
Interaction-ID: 36836

gene/protein

IL1RN

affects_quantity of

gene/protein

IL1B

Drugbank entries Show/Hide entries for IL1B
Comment The interleukin-1 receptor antagonist (IL-1Ra) a physiological antagonist for the IL-1 Receptor is the principal determinant of IL-1beta bioactivity within the IL-1 gene cluster, regulating IL-1alpha and IL-1beta release.
Formal Description
Interaction-ID: 36837

gene/protein

IL1RN

affects_quantity of

gene/protein

IL1A

Comment Proinflammatory cytokines such as IL-1beta and IL-6 are produced not only by the liver but also by the brain.
Formal Description
Interaction-ID: 36846

gene/protein

IL1B

is localized in

tissue/cell line

brain

Drugbank entries Show/Hide entries for IL1B
Comment Proinflammatory cytokines such as IL-1beta and IL-6 are produced not only by the liver but also by the brain.
Formal Description
Interaction-ID: 36851

gene/protein

IL6

is localized in

tissue/cell line

brain

Drugbank entries Show/Hide entries for IL6
Comment Monocyte-derived dendritic cells (MDDCs) from AD patients produce high amounts of IL-6 confirming the proinflammatory features of these cells in AD patients.
Formal Description
Interaction-ID: 36852

affects_activity of

in AD patients
Comment Monocyte-derived dendritic cells (MDDCs) from AD patients produce high amounts of IL-6 confirming the proinflammatory features of these cells in AD patients.
Formal Description
Interaction-ID: 36853

increases_quantity of

gene/protein

IL6

in AD patients
Drugbank entries Show/Hide entries for IL6
Comment AD was associated with low plasma levels of cyanocobalamin (vitamin B12) and low B12 level was associated with greater production of IL-6 in peripheral blood mononuclear cells.
Formal Description
Interaction-ID: 36854

increases_activity of

phenotype

decreased vitamin B12 level

in plasma
Comment AD was associated with low plasma levels of cyanocobalamin (vitamin B12) and low B12 level was associated with greater production of IL-6 in peripheral blood mononuclear cells.
Formal Description
Interaction-ID: 36861

phenotype

decreased vitamin B12 level

increases_quantity of

gene/protein

IL6

in in peripheral blood mononuclear cells
Drugbank entries Show/Hide entries for IL6
Comment The -572C/G (IL-6prom) polymorphism of IL-6 gene promoter region is associated with AD.
Formal Description
Interaction-ID: 36864

gene/protein

IL6 (promoter)

affects_activity of

The IL-6prom G allele might be a risk factor for sporadic AD.
Comment A high cholesterol (HC) diet results in increases in levels of the IL-6, gliosis, astrocytic reactivity and neuroinflammation as well as induce expression of antioxidant enzyme NAD(P)H:quinone oxidoreductase (NQO1) in the hippocampus and cerebral cortex in the brains of wild type (WT) and apolipoprotein E knockout (APOE-/-) mice.
Formal Description
Interaction-ID: 36897

environment

high cholesterol diet

increases_quantity of

gene/protein

IL6

in the hippocampus and cerebral cortex in the brains; of wild type (WT) and apolipoprotein E knockout (APOE-/-) mice
Drugbank entries Show/Hide entries for IL6
Comment A high cholesterol (HC) diet results in increases in levels of the IL-6, gliosis, astrocytic reactivity and neuroinflammation as well as induce expression of antioxidant enzyme NAD(P)H:quinone oxidoreductase (NQO1) in the hippocampus and cerebral cortex in the brains of wild type (WT) and apolipoprotein E knockout (APOE-/-) mice.
Formal Description
Interaction-ID: 36900

environment

high cholesterol diet

increases_activity of

phenotype

gliosis

in the hippocampus and cerebral cortex in the brains; of wild type (WT) and apolipoprotein E knockout (APOE-/-) mice
Comment A high cholesterol (HC) diet results in increases in levels of the IL-6, gliosis, astrocytic reactivity and neuroinflammation as well as induce expression of antioxidant enzyme NAD(P)H:quinone oxidoreductase (NQO1) in the hippocampus and cerebral cortex in the brains of wild type (WT) and apolipoprotein E knockout (APOE-/-) mice.
Formal Description
Interaction-ID: 36903

environment

high cholesterol diet

increases_activity of

in the hippocampus and cerebral cortex in the brains; of wild type (WT) and apolipoprotein E knockout (APOE-/-) mice
Comment A high cholesterol (HC) diet results in increases in levels of the IL-6, gliosis, astrocytic reactivity and neuroinflammation as well as induce expression of antioxidant enzyme NAD(P)H:quinone oxidoreductase (NQO1) in the hippocampus and cerebral cortex in the brains of wild type (WT) and apolipoprotein E knockout (APOE-/-) mice.
Formal Description
Interaction-ID: 36906

environment

high cholesterol diet

increases_activity of

phenotype

neuroinflammation

in the hippocampus and cerebral cortex in the brains; of wild type (WT) and apolipoprotein E knockout (APOE-/-) mice
Comment A high cholesterol (HC) diet results in increases in levels of the IL-6, gliosis, astrocytic reactivity and neuroinflammation as well as induce expression of antioxidant enzyme NAD(P)H:quinone oxidoreductase (NQO1) in the hippocampus and cerebral cortex in the brains of wild type (WT) and apolipoprotein E knockout (APOE-/-) mice.
Formal Description
Interaction-ID: 36910

environment

high cholesterol diet

increases_expression of

gene/protein

NQO1

in the hippocampus and cerebral cortex in the brains; of wild type (WT) and apolipoprotein E knockout (APOE-/-) mice
Drugbank entries Show/Hide entries for NQO1
Comment Rosuvastatin, an inhibitor of the HMG-CoA reductase, prevented the increases in inflammatory microglia and IL-6 levels in the brain and plasma of WT and APOE(-/-) mice.
Formal Description
Interaction-ID: 36912

drug/chemical compound

Rosuvastatin

decreases_quantity of

tissue/cell line

microglia

in the brain and plasma; of WT and APOE(-/-) mice
Drugbank entries Show/Hide entries for Rosuvastatin
Comment Rosuvastatin, an inhibitor of the HMG-CoA reductase, prevented the increases in inflammatory microglia and IL-6 levels in the brain and plasma of WT and APOE(-/-) mice.
Formal Description
Interaction-ID: 36914

drug/chemical compound

Rosuvastatin

decreases_quantity of

gene/protein

IL6

in the brain and plasma; of WT and APOE(-/-) mice
Drugbank entries Show/Hide entries for Rosuvastatin or IL6
Comment IL-18 is a potent proinflammatory cytokine of the IL-1 superfamily.
Formal Description
Interaction-ID: 36916

gene/protein

IL18

affects_activity of

gene/protein

Proinflammatory cytokine

and member of the IL-1 superfamily
Comment IL-18 is cleaved by caspase-1 (ICE) to an active secreted form.
Formal Description
Interaction-ID: 36918

gene/protein

CASP1

increases_processing of

gene/protein

IL18

to an active secreted form
Drugbank entries Show/Hide entries for CASP1
Comment IL-18 is cleaved by caspase-1 (ICE) to an active secreted form.
Formal Description
Interaction-ID: 36920

gene/protein

CASP1

increases_quantity of

by cleaving IL-18
Drugbank entries Show/Hide entries for CASP1
Comment IL-18 acts through a heterodimer receptor comprised of a subunit alpha (IL-18Ralpha) required for binding, and a subunit beta (IL-18Rbeta) necessary for activation of signal transduction.
Formal Description
Interaction-ID: 36924

gene/protein

IL18R1

interacts (colocalizes) with

gene/protein

IL18RAP

and act as a heterodimer receptor via IL18
Comment IL-18 acts through a heterodimer receptor comprised of a subunit alpha (IL-18Ralpha) required for binding, and a subunit beta (IL-18Rbeta) necessary for activation of signal transduction.
Formal Description
Interaction-ID: 36931

gene/protein

IL18

interacts (colocalizes) with

gene/protein

IL18RAP

Comment IL-18 acts through a heterodimer receptor comprised of a subunit alpha (IL-18Ralpha) required for binding, and a subunit beta (IL-18Rbeta) necessary for activation of signal transduction.
Formal Description
Interaction-ID: 36932

gene/protein

IL18

interacts (colocalizes) with

gene/protein

IL18R1

Comment In AD, IL-18 is co-localized not only with Abeta plaques but also with tau. The Abeta may induce the synthesis of IL-18, and IL-18 kinases involved in tau phosphorylation as a part of the amyloid-associated inflammatory reaction.
Formal Description
Interaction-ID: 36933

gene/protein

IL18

interacts (colocalizes) with

gene/protein

Amyloid beta peptide

Comment In AD, IL-18 is co-localized not only with Abeta plaques but also with tau. The Abeta may induce the synthesis of IL-18, and IL-18 kinases involved in tau phosphorylation as a part of the amyloid-associated inflammatory reaction.
Formal Description
Interaction-ID: 36934

gene/protein

IL18

interacts (colocalizes) with

gene/protein

MAPT

Comment In the CNS, IL-18 is produced by microglial, astrocytes and ependymal cells as well as by neurons of the medial habenular nucleus.
Formal Description
Interaction-ID: 36935

tissue/cell line

microglia

increases_quantity of

gene/protein

IL18

Comment In the CNS, IL-18 is produced by microglial, astrocytes and ependymal cells as well as by neurons of the medial habenular nucleus.
Formal Description
Interaction-ID: 36936

tissue/cell line

astrocyte

increases_quantity of

gene/protein

IL18

Comment In the CNS, IL-18 is produced by microglial, astrocytes and ependymal cells as well as by neurons of the medial habenular nucleus.
Formal Description
Interaction-ID: 36937

tissue/cell line

ependymoma cell

increases_quantity of

gene/protein

IL18

Comment In the CNS, IL-18 is produced by microglial, astrocytes and ependymal cells as well as by neurons of the medial habenular nucleus.
Formal Description
Interaction-ID: 36938

tissue/cell line

medial habenular nucleus

increases_quantity of

gene/protein

IL18

by neurons of the medial habenular nucleus
Comment The levels of total-RNA and protein of IL-18 and ICE increases, especially in the frontal lobe of AD patients.
Formal Description
Interaction-ID: 36939

increases_quantity of

gene/protein

IL18

in the frontal lobe; of AD patients
Comment The levels of total-RNA and protein of IL-18 and ICE increases, especially in the frontal lobe of AD patients.
Formal Description
Interaction-ID: 36940

increases_quantity of

gene/protein

CASP1

in the frontal lobe; of AD patients
Drugbank entries Show/Hide entries for CASP1
Comment In CSF elevated IL-18 level was detected only in men and it also correlated with CSF tau in MCI.
Formal Description
Interaction-ID: 36941

phenotype

sex, male

increases_quantity of

gene/protein

IL18

in CSF; elevated IL-18 level was detected only in men.
Comment A significant correlation between IL-18 production and cognitive decline was observed in AD patients.
Formal Description
Interaction-ID: 36944

phenotype

increased IL18 level

cooccurs with

phenotype

cognitive impairment

in AD patients
Comment IFN-gamma has a strong suppressive effect on the production and metabolism of APP.
Formal Description
Interaction-ID: 36945

gene/protein

IFNG

affects_quantity of

gene/protein

APP

Drugbank entries Show/Hide entries for IFNG or APP
Comment IFN-gamma has a strong suppressive effect on the production and metabolism of APP.
Formal Description
Interaction-ID: 36949

gene/protein

IFNG

decreases_activity of

Drugbank entries Show/Hide entries for IFNG
Comment IFN-gamma reverses the increase in oligodendrogenesis in a mouse model of AD.
Formal Description
Interaction-ID: 36950

gene/protein

IFNG

affects_activity of

phenotype

oligodendrogenesis

Drugbank entries Show/Hide entries for IFNG
Comment Elevated levels of the TNF have been reported in serum and postmortem brains of patients with AD.
Formal Description
Interaction-ID: 36954

increases_quantity of

gene/protein

TNF

in serum and postmortem brains of AD patients
Drugbank entries Show/Hide entries for TNF
Comment Soluble TNF is a critical mediator of the effects of neuroinflammation on early (preplaque) pathology in 3xTg-AD mice, a murine model of AD which develop both amyloid plaque and neurofibrillary tangle pathologies. In AD, targeted inhibition of solTNF in the CNS may slow the appearance of amyloid-associated pathology, cognitive deficits, and potentially the progressive loss of neurons.
Formal Description
Interaction-ID: 36956

gene/protein

TNF (soluble)

affects_activity of

phenotype

neuroinflammation

on early (preplaque) pathology in 3xTg-AD mice
Comment Soluble TNF (sTNF) is part of TNF (tumor necrosis factor) and a multifunctional proinflammatory cytokine.
Formal Description
Interaction-ID: 36957

gene/protein

TNF (soluble)

affects_activity of

gene/protein

Proinflammatory cytokine

Comment TNF-alpha is released from cell membranes by the TNFalpha-converting enzyme (TACE). Inhibition of TACE has potential to mitigate TNFalpha effects in AD brain.
Formal Description
Interaction-ID: 36959

gene/protein

ADAM17

affects_quantity of

gene/protein

TNF

via releasing TNF-alpha from cell membranes
Drugbank entries Show/Hide entries for ADAM17 or TNF
Comment Hypothesis: TNF-alpha gene G-308A polymorphism might be a risk factor for late-onset AD (LOAD) and dependent on APOE epsilon4 status in china population. Some data support an association between TNF-alpha-850 C/T polymorphism and the risk of AD.
Formal Description
Interaction-ID: 36964

none selected

Drugbank entries Show/Hide entries for or
Comment TNFR1 is expressed in most cell types, and can be activated by binding of either solTNF or transmembrane TNF (tmTNF), with a preference for solTNF.
Formal Description
Interaction-ID: 36967

gene/protein

TNF (soluble)

increases_activity of

gene/protein

TNFRSF1A

Drugbank entries Show/Hide entries for TNFRSF1A
Comment TNFR1 is expressed in most cell types, and can be activated by binding of either solTNF or transmembrane TNF (tmTNF), with a preference for solTNF.
Formal Description
Interaction-ID: 36991

gene/protein

TNF (transmembrane)

increases_activity of

gene/protein

TNFRSF1A

Drugbank entries Show/Hide entries for TNFRSF1A
Comment TNFR2 is expressed primarily by microglia and endothelial cells and is preferentially activated by tmTNF.
Formal Description
Interaction-ID: 36996

gene/protein

TNFRSF1B

is_expressed_in

tissue/cell line

microglia

Drugbank entries Show/Hide entries for TNFRSF1B
Comment TNFR2 is expressed primarily by microglia and endothelial cells and is preferentially activated by tmTNF.
Formal Description
Interaction-ID: 36997

gene/protein

TNFRSF1B

is_expressed_in

tissue/cell line

endothelial cell

Drugbank entries Show/Hide entries for TNFRSF1B
Comment TNFR2 is expressed primarily by microglia and endothelial cells and is preferentially activated by tmTNF.
Formal Description
Interaction-ID: 36998

gene/protein

TNF (transmembrane)

increases_activity of

gene/protein

TNFRSF1B

Drugbank entries Show/Hide entries for TNFRSF1B
Comment Both TNFR1 and TNFR2 are expressed in neurons in AD and non-demented brains. TNFR1 levels are increased but TNFR2 levels are decreased in AD brains compared to non-demented brains.
Formal Description
Interaction-ID: 36999

gene/protein

TNFRSF1A

is_expressed_in

tissue/cell line

neuron

in AD and non-demented brains
Drugbank entries Show/Hide entries for TNFRSF1A
Comment Both TNFR1 and TNFR2 are expressed in neurons in AD and non-demented brains. TNFR1 levels are increased but TNFR2 levels are decreased in AD brains compared to non-demented brains.
Formal Description
Interaction-ID: 37000

gene/protein

TNFRSF1B

is_expressed_in

tissue/cell line

neuron

in AD and non-demented brains
Drugbank entries Show/Hide entries for TNFRSF1B
Comment TNFR1 contains a cytoplasmic death domain that required for neuronal death induced by Abeta protein in the AD brain.
Formal Description
Interaction-ID: 37003

gene/protein

TNFRSF1A

affects_activity of

process

neuron death

via a cytoplasmic death domain in TNFR1, induced by Abeta protein in the AD brain
Drugbank entries Show/Hide entries for TNFRSF1A
Comment Genetic deletion of TNFR1 leads to reduced BACE1 levels and activity, because TNFR1 regulates BACE1 promoter activity via the NF-kappaB pathway.
Formal Description
Interaction-ID: 37070

gene/protein

TNFRSF1A

increases_quantity of

gene/protein

BACE1

TNFR1 regulates BACE1 promoter activity via the NF-kappaB pathway.
Drugbank entries Show/Hide entries for TNFRSF1A or BACE1
Comment Genetic deletion of TNFR1 leads to reduced BACE1 levels and activity, because TNFR1 regulates BACE1 promoter activity via the NF-kappaB pathway.
Formal Description
Interaction-ID: 37071

gene/protein

TNFRSF1A

increases_activity of

gene/protein

BACE1 (promoter)

via the NF-kappaB pathway.
Drugbank entries Show/Hide entries for TNFRSF1A
Comment TRAIL is specifically expressed in the brain of AD patients and completely absent in the brain of non-demented patients and promotes apoptosis of parenchymal cells through interaction with TRAIL death receptor 5 (DR5) expressed in neurons.
Formal Description
Interaction-ID: 37072

increases_expression of

gene/protein

TNFSF10

TRAIL / TNFSF10 is completely absent in the brain of non-demented patients
Comment TRAIL is specifically expressed in the brain of AD patients and completely absent in the brain of non-demented patients and promotes apoptosis of parenchymal cells through interaction with TRAIL death receptor 5 (DR5) expressed in neurons.
Formal Description
Interaction-ID: 37073

gene/protein

TNFSF10

increases_activity of

of parenchymal cells
Comment TRAIL is specifically expressed in the brain of AD patients and completely absent in the brain of non-demented patients and promotes apoptosis of parenchymal cells through interaction with TRAIL death receptor 5 (DR5) expressed in neurons.
Formal Description
Interaction-ID: 37077

gene/protein

TNFSF10

interacts (colocalizes) with

gene/protein

TNFRSF10B

in neurons
Comment TRAIL is specifically expressed in the brain of AD patients and completely absent in the brain of non-demented patients and promotes apoptosis of parenchymal cells through interaction with TRAIL death receptor 5 (DR5) expressed in neurons.
Formal Description
Interaction-ID: 37080

gene/protein

TNFRSF10B

is_expressed_in

tissue/cell line

neuron

Comment DR5 is demonstrated to be a key factor in TRAIL death pathway.
Formal Description
Interaction-ID: 37090

gene/protein

TNFRSF10B

affects_activity of

complex/PPI

TRAIL death-inducing signaling complex

Comment DR5 is demonstrated to be a key factor in TRAIL death pathway.
Formal Description
Interaction-ID: 37095

gene/protein

TNFRSF10B

affects_activity of

complex/PPI

TRAIL death-inducing signaling complex

Comment Infliximab is able to reduce the levels of TNF-alpha, amyloid plaques, and tau phosphorylation.
Formal Description
Interaction-ID: 37111

drug/chemical compound

Infliximab

decreases_quantity of

gene/protein

TNF

Drugbank entries Show/Hide entries for Infliximab or TNF
Comment Infliximab is able to reduce the levels of TNF-alpha, amyloid plaques, and tau phosphorylation.
Formal Description
Interaction-ID: 37118

drug/chemical compound

Infliximab

decreases_quantity of

Drugbank entries Show/Hide entries for Infliximab
Comment Infliximab is able to reduce the levels of TNF-alpha, amyloid plaques, and tau phosphorylation.
Formal Description
Interaction-ID: 37119

drug/chemical compound

Infliximab

decreases_quantity of

protein modification

MAPT-phos

Drugbank entries Show/Hide entries for Infliximab
Comment IL-34 promoted microglial proliferation and clearance of soluble oligomeric amyloid-beta (oAbeta), increased the expression of IDE, and induced the antioxidant enzyme heme oxygenase-1 in microglia to reduce oxidative stress, without producing neurotoxic molecules.
Formal Description
Interaction-ID: 37123

gene/protein

IL34

increases_quantity of

tissue/cell line

microglia

microglial proliferation was increased
Comment IL-34 promoted microglial proliferation and clearance of soluble oligomeric amyloid-beta (oAbeta), increased the expression of IDE, and induced the antioxidant enzyme heme oxygenase-1 in microglia to reduce oxidative stress, without producing neurotoxic molecules.
Formal Description
Interaction-ID: 37159

gene/protein

IL34

decreases_quantity of

complex/PPI

Amyloid beta peptide (oligomer, soluble)

Comment IL-34 promoted microglial proliferation and clearance of soluble oligomeric amyloid-beta (oAbeta), increased the expression of IDE, and induced the antioxidant enzyme heme oxygenase-1 in microglia to reduce oxidative stress, without producing neurotoxic molecules.
Formal Description
Interaction-ID: 37166

gene/protein

IL34

increases_expression of

gene/protein

IDE

Drugbank entries Show/Hide entries for IDE
Comment IL-34 promoted microglial proliferation and clearance of soluble oligomeric amyloid-beta (oAbeta), increased the expression of IDE, and induced the antioxidant enzyme heme oxygenase-1 in microglia to reduce oxidative stress, without producing neurotoxic molecules.
Formal Description
Interaction-ID: 37172

gene/protein

IL34

increases_expression of

gene/protein

HMOX1

in microglia
Drugbank entries Show/Hide entries for HMOX1
Comment IL-34 promoted microglial proliferation and clearance of soluble oligomeric amyloid-beta (oAbeta), increased the expression of IDE, and induced the antioxidant enzyme heme oxygenase-1 in microglia to reduce oxidative stress, without producing neurotoxic molecules.
Formal Description
Interaction-ID: 37175

gene/protein

IL34

affects_activity of

Comment TGF-beta2 are elevated in cells which mainly consisting of neurons of both hippocampi and cerebral cortices of human AD brains.
Formal Description
Interaction-ID: 37180

increases_quantity of

gene/protein

TGFB2

in cells which mainly consisting of neurons of both hippocampi and cerebral cortices of human AD brains
Comment The expression of TGFbeta2 is induced by toxic Abeta in both glial and neuronal cells.
Formal Description
Interaction-ID: 37183

increases_expression of

gene/protein

TGFB2

in both glial and neuronal cells
Comment Increased levels of TGFbeta2 are triggered in a neuronal cell death pathway related to AD by binding to the extracellular domain of APP on the cell surface and by triggering an intracellular death signal pathway, mediated by a heterotrimeric G protein Go, Rac1/cdc42, ASK1, JNK, NADPH oxidase and caspases.
Formal Description
Interaction-ID: 37192

gene/protein

TGFB2

interacts (colocalizes) with

gene/protein

APP

by binding to the extracellular domain of APP on the cell surface and mediated by a heterotrimeric G protein Go, Rac1/cdc42, ASK1, JNK, NADPH oxidase and caspases
Drugbank entries Show/Hide entries for APP
Comment TGF-beta2 alters the morphology and numbers of lysosomes in neurons.
Formal Description
Interaction-ID: 37203

gene/protein

TGFB2

affects_quantity of

cellular component

lysosome

in neurons; and also morphology of lysosomes
Comment TGF-beta2 makes unstable and leaky lysosomal membranes and this effect is exacerbated with the addition of Abeta, because TGF-beta2 rapidly targets Abeta peptide in lysosomal compartment in cortical neurons and induces cell death.
Formal Description
Interaction-ID: 37205

gene/protein

TGFB2

increases_activity of

TGF-beta2 makes unstable and leaky lysosomal membranes.
Comment TGF-beta2 makes unstable and leaky lysosomal membranes and this effect is exacerbated with the addition of Abeta, because TGF-beta2 rapidly targets Abeta peptide in lysosomal compartment in cortical neurons and induces cell death.
Formal Description
Interaction-ID: 37207

gene/protein

TGFB2

increases_activity of

process

neuron death

Comment TGF-beta2 makes unstable and leaky lysosomal membranes and this effect is exacerbated with the addition of Abeta, because TGF-beta2 rapidly targets Abeta peptide in lysosomal compartment in cortical neurons and induces cell death.
Formal Description
Interaction-ID: 37208

gene/protein

TGFB2

interacts (colocalizes) with

gene/protein

Amyloid beta peptide

in lysosomal compartment in cortical neurons; and induces cell death
Comment The transient axonal glycoprotein-1 (TAG-1), a glycophosphatidylinositol-linked protein, is another natural ligand of APP and inhibits TGF-beta2-mediated neuronal cell death via APP by attenuating the binding of TGF-beta2 to APP in a gamma-secretase-independent manner.
Formal Description
Interaction-ID: 37209

gene/protein

CNTN2

interacts (colocalizes) with

gene/protein

APP

Drugbank entries Show/Hide entries for APP
Comment The transient axonal glycoprotein-1 (TAG-1), a glycophosphatidylinositol-linked protein, is another natural ligand of APP and inhibits TGF-beta2-mediated neuronal cell death via APP by attenuating the binding of TGF-beta2 to APP in a gamma-secretase-independent manner.
Formal Description
Interaction-ID: 37210

gene/protein

CNTN2

decreases_activity of

gene/protein

TGFB2

by attenuating the binding of TGF-beta2 to APP
Comment Upregulation of the TGFbeta2 level is a common pathological feature of AD brains and suggests that it may be closely linked to the development of neuronal death related to AD.
Formal Description
Interaction-ID: 37211

increases_expression of

gene/protein

TGFB2

in AD brain
Comment TGF-beta1 can be protective in AD.
Formal Description
Interaction-ID: 37216

gene/protein

TGFB1

decreases_activity of

Drugbank entries Show/Hide entries for TGFB1
Comment TGF-beta type II receptor (TBRII) is mainly expressed by neurons, and its expression is reduced very early in the course of AD. In cultured cells, reduced TGF-beta signaling caused neuronal degeneration and resulted in increased levels of secreted Abeta and beta-secretase-cleaved soluble APP.
Formal Description
Interaction-ID: 37219

decreases_expression of

gene/protein

TGFBR2

Drugbank entries Show/Hide entries for TGFBR2
Comment TGF-beta type II receptor (TBRII) is mainly expressed by neurons, and its expression is reduced very early in the course of AD. In cultured cells, reduced TGF-beta signaling caused neuronal degeneration and resulted in increased levels of secreted Abeta and beta-secretase-cleaved soluble APP.
Formal Description
Interaction-ID: 37220

tissue/cell line

neuron

increases_expression of

gene/protein

TGFBR2

Drugbank entries Show/Hide entries for TGFBR2
Comment Some data report that TGF-beta1 and nuclear Smad7 and beta-catenin levels are markedly upregulate in cortical brain regions of the TgCRND8 mice, a mouse model of familial AD, and this high brain level of Abeta and TGF-beta1 have been implicated in the cognitive and cerebrovascular alterations of AD.
Formal Description
Interaction-ID: 37230

increases_expression of

gene/protein

TGFB1

in cortical brain regions; of the TgCRND8 mice, a mouse model of familial AD
Drugbank entries Show/Hide entries for TGFB1
Comment Some data report that TGF-beta1 and nuclear Smad7 and beta-catenin levels are markedly upregulate in cortical brain regions of the TgCRND8 mice, a mouse model of familial AD, and this high brain level of Abeta and TGF-beta1 have been implicated in the cognitive and cerebrovascular alterations of AD.
Formal Description
Interaction-ID: 37232

increases_expression of

gene/protein

SMAD7

in cortical brain regions; of the TgCRND8 mice, a mouse model of familial AD
Comment Some data report that TGF-beta1 and nuclear Smad7 and beta-catenin levels are markedly upregulate in cortical brain regions of the TgCRND8 mice, a mouse model of familial AD, and this high brain level of Abeta and TGF-beta1 have been implicated in the cognitive and cerebrovascular alterations of AD.
Formal Description
Interaction-ID: 37233

increases_expression of

gene/protein

CTNNB1

in cortical brain regions; of the TgCRND8 mice, a mouse model of familial AD
Drugbank entries Show/Hide entries for CTNNB1
Comment Some data report that TGF-beta1 and nuclear Smad7 and beta-catenin levels are markedly upregulate in cortical brain regions of the TgCRND8 mice, a mouse model of familial AD, and this high brain level of Abeta and TGF-beta1 have been implicated in the cognitive and cerebrovascular alterations of AD.
Formal Description
Interaction-ID: 37234

increases_activity of

in cortical brain regions; of the TgCRND8 mice, a mouse model of familial AD
Comment Increased brain levels of TGF-beta1 induce a vascular pathology.
Formal Description
Interaction-ID: 37235

gene/protein

TGFB1

increases_activity of

in brain; if TGFB1 is increased
Drugbank entries Show/Hide entries for TGFB1
Comment The antiinflammatory cytokines IL-4 and IL-13 effectively enhanced expression of the CD36 and Abeta-degrading enzymes by microglia.
Formal Description
Interaction-ID: 37254

gene/protein

IL4

increases_expression of

gene/protein

CD36

Comment The antiinflammatory cytokines IL-4 and IL-13 effectively enhanced expression of the CD36 and Abeta-degrading enzymes by microglia.
Formal Description
Interaction-ID: 37255

gene/protein

IL13

increases_expression of

gene/protein

CD36

Comment The major Abeta-degrading enzymes are neprilysin (NEP), insulin-degrading enzyme (IDE), and endothelin-converting enzyme (ECE-1).
Formal Description
Interaction-ID: 37258

gene/protein

MME

decreases_quantity of

gene/protein

Amyloid beta peptide

in type 2 microglia; by degrading Abeta
Drugbank entries Show/Hide entries for MME
Comment The major Abeta-degrading enzymes are neprilysin (NEP), insulin-degrading enzyme (IDE), and endothelin-converting enzyme (ECE-1).
Formal Description
Interaction-ID: 37271

gene/protein

IDE

decreases_quantity of

gene/protein

Amyloid beta peptide

by degrading Abeta
Drugbank entries Show/Hide entries for IDE
Comment The major Abeta-degrading enzymes are neprilysin (NEP), insulin-degrading enzyme (IDE), and endothelin-converting enzyme (ECE-1).
Formal Description
Interaction-ID: 37274

gene/protein

ECE1

decreases_quantity of

gene/protein

Amyloid beta peptide

by degrading Abeta
Drugbank entries Show/Hide entries for ECE1
Comment IL-4 stimulates uptake of Abeta by CD36, and increases expression of NEP as the major protease involved in Abeta degradation in type 2, but not type 1 microglia that express CD40, which suggests the two microglia types may play different neuroimmunomodulating roles in the Abeta-overproducing brain.
Formal Description
Interaction-ID: 37275

gene/protein

IL4

increases_activity of

process

protein import

of Abeta by CD36
Comment IL-4 stimulates uptake of Abeta by CD36, and increases expression of NEP as the major protease involved in Abeta degradation in type 2, but not type 1 microglia that express CD40, which suggests the two microglia types may play different neuroimmunomodulating roles in the Abeta-overproducing brain.
Formal Description
Interaction-ID: 37282

gene/protein

IL4

increases_expression of

gene/protein

MME

Drugbank entries Show/Hide entries for MME
Comment IL-4 stimulates uptake of Abeta by CD36, and increases expression of NEP as the major protease involved in Abeta degradation in type 2, but not type 1 microglia that express CD40, which suggests the two microglia types may play different neuroimmunomodulating roles in the Abeta-overproducing brain.
Formal Description
Interaction-ID: 37288

tissue/cell line

microglia

increases_expression of

gene/protein

CD40

(M1 subtype microglia cells)
Comment Treatment of microglia and macrophages with IL-4 and IL-13 significantly increased expression of CD200R.
Formal Description
Interaction-ID: 37290

gene/protein

IL4

increases_expression of

gene/protein

CD200R1

Comment Treatment of microglia and macrophages with IL-4 and IL-13 significantly increased expression of CD200R.
Formal Description
Interaction-ID: 37293

gene/protein

IL13

increases_expression of

gene/protein

CD200R1

Comment IL-4 generates microglial NADPH oxidase-derived oxidative stress and leads to the degeneration of hippocampal neurons in vivo.
Formal Description
Interaction-ID: 37294

gene/protein

IL4

increases_activity of

IL-4 generates microglial NADPH oxidase-derived oxidative stress
Comment IL-4 generates microglial NADPH oxidase-derived oxidative stress and leads to the degeneration of hippocampal neurons in vivo.
Formal Description
Interaction-ID: 37297

gene/protein

IL4

increases_activity of

phenotype

neurodegeneration

in hippocampus
Comment NADPH oxidase expression is upregulated in AD and is an essential component of microglia-mediated Abeta neurotoxicity.
Formal Description
Interaction-ID: 37298

increases_expression of

complex/PPI

NADPH oxidase complex

Comment Oligomeric Abeta stimulates the production of ROS in neurons through an NMDA (N-methyl-d-aspartate)-dependent pathway.
Formal Description
Interaction-ID: 37299

complex/PPI

Amyloid beta peptide (oligomer)

increases_quantity of

drug/chemical compound

Reactive oxygen species

in neurons; through an NMDA (N-methyl-d-aspartate)-dependent pathway
Comment Activation of microglial NADPH oxidase causes neurotoxicity through two mechanisms: (1) extracellular ROS produced by microglia which are directly toxic to neurons, and (2) intracellular ROS function as a signaling mechanism in microglia to amplify the production of several proinflammatory and neurotoxic cytokines (such as TNF-alpha, prostaglandin E2, and IL-1beta).
Formal Description
Interaction-ID: 37301

complex/PPI

NADPH oxidase complex

affects_activity of

process

neuron death

in microglia; via neurotoxicity.
Comment The antiinflammatory cytokine IL-10 can inhibit both cytokine and chemokine production in the brain.
Formal Description
Interaction-ID: 37302

gene/protein

IL10

decreases_quantity of

gene/protein

Cytokine

in brain
Comment IL-10 causes a dose-dependent inhibition of the IL-6 secretion induced by Abeta in glial cells.
Formal Description
Interaction-ID: 37304

gene/protein

IL10

decreases_quantity of

gene/protein

IL6

in glial cells; induced by Abeta
Drugbank entries Show/Hide entries for IL6
Comment IL-10 elicits a strong and weak increase in STAT3 and STAT1 phosphorylation, respectively, in human T lymphocyte, suggesting that STAT3 is a main IL-10 signaling event in these cells. IL-10 failed to induce STAT3 in glial cells, but only elicited a weak increase in STAT1 phosphorylation in microglia.
Formal Description
Interaction-ID: 37311

gene/protein

IL10

increases_phosphorylation of

gene/protein

STAT3

in human T lymphocyte; IL-10 failed to induce STAT3 in glial cells.
Comment IL-10 is highly polymorphic, and its production is correlated to biallelic polymorphisms at positions -1082 (G to A), -819 (T to C), and -592 (A to C). The homozygosis for the A allele of -1082 polymorphism (G/A) of IL-10 promotes a higher risk of AD and reduces IL-10 generation in peripheral cells after amyloid stimulation.
Formal Description
Interaction-ID: 37312

gene/protein mutant

IL10-mut

increases_activity of

in peripheral cells; the homozygosis for the A allele of -1082 polymorphism (G/A) of IL-10 promotes a higher risk of AD and reduces IL-10 generation
Comment Activation of microglial NADPH oxidase causes neurotoxicity through two mechanisms: (1) extracellular ROS produced by microglia which are directly toxic to neurons, and (2) intracellular ROS function as a signaling mechanism in microglia to amplify the production of several proinflammatory and neurotoxic cytokines.
Formal Description
Interaction-ID: 37317

tissue/cell line

microglia

increases_quantity of

drug/chemical compound

Reactive oxygen species

extracellular ROS is toxic to neurons
Comment Activation of microglial NADPH oxidase causes neurotoxicity through two mechanisms: (1) extracellular ROS produced by microglia which are directly toxic to neurons, and (2) intracellular ROS function as a signaling mechanism in microglia to amplify the production of several proinflammatory and neurotoxic cytokines.
Formal Description
Interaction-ID: 37321

drug/chemical compound

Reactive oxygen species

increases_activity of

phenotype

neuroinflammation

via extracellular ROS produced by microglia
Comment Activation of microglial NADPH oxidase causes neurotoxicity through two mechanisms: (1) extracellular ROS produced by microglia which are directly toxic to neurons, and (2) intracellular ROS function as a signaling mechanism in microglia to amplify the production of several proinflammatory and neurotoxic cytokines (such as TNF-alpha, prostaglandin E2, and IL-1beta).
Formal Description
Interaction-ID: 37323

drug/chemical compound

Reactive oxygen species

increases_quantity of

gene/protein

Proinflammatory cytokine

in microglia; such as TNF-alpha, prostaglandin E2, and IL-1beta
Comment Activation of microglial NADPH oxidase causes neurotoxicity through two mechanisms: (1) extracellular ROS produced by microglia which are directly toxic to neurons, and (2) intracellular ROS function as a signaling mechanism in microglia to amplify the production of several proinflammatory and neurotoxic cytokines (such as TNF-alpha, prostaglandin E2, and IL-1beta).
Formal Description
Interaction-ID: 37326

drug/chemical compound

Reactive oxygen species

increases_quantity of

gene/protein

TNF

in microglia
Drugbank entries Show/Hide entries for TNF
Comment Activation of microglial NADPH oxidase causes neurotoxicity through two mechanisms: (1) extracellular ROS produced by microglia which are directly toxic to neurons, and (2) intracellular ROS function as a signaling mechanism in microglia to amplify the production of several proinflammatory and neurotoxic cytokines (such as TNF-alpha, prostaglandin E2, and IL-1beta).
Formal Description
Interaction-ID: 37328

drug/chemical compound

Reactive oxygen species

increases_quantity of

drug/chemical compound

Prostaglandin E2

in microglia
Comment Activation of microglial NADPH oxidase causes neurotoxicity through two mechanisms: (1) extracellular ROS produced by microglia which are directly toxic to neurons, and (2) intracellular ROS function as a signaling mechanism in microglia to amplify the production of several proinflammatory and neurotoxic cytokines (such as TNF-alpha, prostaglandin E2, and IL-1beta).
Formal Description
Interaction-ID: 37330

drug/chemical compound

Reactive oxygen species

increases_quantity of

gene/protein

IL1B

in microglia
Drugbank entries Show/Hide entries for IL1B
Comment The antiinflammatory cytokine IL-10 can inhibit both cytokine and chemokine production in the brain.
Formal Description
Interaction-ID: 37333

gene/protein

IL10

decreases_quantity of

gene/protein

Chemokine

in brain
Comment IL-10 elicits a strong and weak increase in STAT3 and STAT1 phosphorylation, respectively, in human T lymphocyte, suggesting that STAT3 is a main IL-10 signaling event in these cells. IL-10 failed to induce STAT3 in glial cells, but only elicited a weak increase in STAT1 phosphorylation in microglia.
Formal Description
Interaction-ID: 37336

gene/protein

IL10

increases_phosphorylation of

gene/protein

STAT1

in human T lymphocyte; and with only a weak increase in STAT1 phosphorylation in microglia
Comment TRAIL is specifically expressed in the brain of AD patients and completely absent in the brain of non-demented patients and promotes apoptosis of parenchymal cells through interaction with TRAIL death receptor 5 (DR5) expressed in neurons.
Formal Description
Interaction-ID: 47950

gene/protein

TNFSF10

is_expressed_in

tissue/cell line

brain

of AD patients
Comment Activation of microglial NADPH oxidase causes neurotoxicity through two mechanisms: (1) extracellular ROS produced by microglia which are directly toxic to neurons, and (2) intracellular ROS function as a signaling mechanism in microglia to amplify the production of several proinflammatory and neurotoxic cytokines.
Formal Description
Interaction-ID: 48849

drug/chemical compound

Reactive oxygen species

increases_activity of

intracellular ROS function as a signaling mechanism in microglia
Comment Activation of microglial NADPH oxidase causes neurotoxicity through two mechanisms: (1) extracellular ROS produced by microglia which are directly toxic to neurons, and (2) intracellular ROS function as a signaling mechanism in microglia to amplify the production of several proinflammatory and neurotoxic cytokines.
Formal Description
Interaction-ID: 64583

increases_activity of

complex/PPI

NADPH oxidase complex

Comment fAbeta binds to CD36 a type B scavenger receptor, and initiate a signaling cascade that regulates microglial recruitment, activation, and secretion of inflammatory mediators leading to neuronal dysfunction and death.
Formal Description
Interaction-ID: 80170

complex/PPI

Amyloid beta peptide (fibrillar)

increases_activity of

that regulates microglial recruitment, activation, and secretion of inflammatory mediators
Comment fAbeta binds to CD36 a type B scavenger receptor, and initiate a signaling cascade that regulates microglial recruitment, activation, and secretion of inflammatory mediators leading to neuronal dysfunction and death.
Formal Description
Interaction-ID: 80171

complex/PPI

Amyloid beta peptide (fibrillar)

increases_activity of

via binding to CD36, a type B scavenger receptor
Comment Genetic deletion of TNFR1 leads to reduced BACE1 levels and activity, because TNFR1 regulates BACE1 promoter activity via the NF-kappaB pathway.
Formal Description
Interaction-ID: 82431

gene/protein

TNFRSF1A

increases_activity of

gene/protein

BACE1

TNFR1 regulates BACE1 promoter activity via the NF-kappaB pathway.
Drugbank entries Show/Hide entries for TNFRSF1A or BACE1