General Information:

Id: 1,184
Diseases: Alzheimer disease - [OMIM]
Chronic granulomatous disease
Mammalia
review
Reference: Wilkinson BL and Landreth GE(2006) The microglial NADPH oxidase complex as a source of oxidative stress in Alzheimers disease J Neuroinflammation 3: 30 [PMID: 17094809]

Interaction Information:

Comment Alzheimer's disease is the most common cause of dementia in the elderly, and manifests as progressive cognitive decline and profound neuronal loss.
Formal Description
Interaction-ID: 7839

phenotype

senility

increases_activity of

Comment Plaques of AD patients are surrounded by activated microglia, which are largely responsible for the proinflammatory environment within the diseased brain.
Formal Description
Interaction-ID: 7844

interacts (colocalizes) with

tissue/cell line

microglia

Comment Senile plaques of AD patients are surrounded by activated microglia, which are largely responsible for the proinflammatory environment within the diseased brain.
Formal Description
Interaction-ID: 7845

increases_activity of

within the diseased brain
Comment Microglia are the resident innate immune cells in the brain.
Formal Description
Interaction-ID: 7855

tissue/cell line

microglia

affects_activity of

Comment In response to contact with fibrillar beta-amyloid, microglia secrete a diverse array of proinflammatory molecules.
Formal Description
Interaction-ID: 7856

complex/PPI

Amyloid beta peptide (fibrillar)

increases_activity of

Comment In response to contact with fibrillar beta-amyloid, microglia secrete a diverse array of proinflammatory molecules.
Formal Description
Interaction-ID: 7857

complex/PPI

Amyloid beta peptide (fibrillar)

increases_activity of

tissue/cell line

microglia

Comment In response to contact with fibrillar beta-amyloid, microglia secrete a diverse array of proinflammatory molecules.
Formal Description
Interaction-ID: 7858

complex/PPI

Amyloid beta peptide (fibrillar)

increases_activity of

Comment The source of fibrillar beta-amyloid induced reactive oxygen species is primarily the microglial nicotinamide adenine dinucleotide phosphate (NADPH) oxidase.
Formal Description
Interaction-ID: 7859

complex/PPI

Amyloid beta peptide (fibrillar)

increases_quantity of

drug/chemical compound

Reactive oxygen species

Comment The source of fibrillar beta-amyloid induced reactive oxygen species is primarily the microglial nicotinamide adenine dinucleotide phosphate (NADPH) oxidase.
Formal Description
Interaction-ID: 7860

complex/PPI

NADPH oxidase complex

increases_quantity of

drug/chemical compound

Reactive oxygen species

in microglia; via amyloid beta peptide
Comment The principal neuropathological hallmarks of Alzheimer's disease are the senile plaques and the neurofibrillary tangles.
Formal Description
Interaction-ID: 7861

increases_quantity of

complex/PPI

Amyloid beta peptide (fibrillar)

Comment The principal neuropathological hallmarks of Alzheimer's disease are the senile plaques and the neurofibrillary tangles.
Formal Description
Interaction-ID: 7862

increases_quantity of

Comment The NADPH oxidase is a multicomponent enzyme complex that, upon activation, produces the highly reactive free radical superoxide.
Formal Description
Interaction-ID: 7863

complex/PPI

NADPH oxidase complex

increases_quantity of

drug/chemical compound

O2-

Comment The source of fibrillar beta-amyloid induced reactive oxygen species is primarily the microglial nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. The NADPH oxidase is a multicomponent enzyme complex that, upon activation, produces the highly reactive free radical superoxide.
Formal Description
Interaction-ID: 7864

complex/PPI

Amyloid beta peptide (fibrillar)

increases_activity of

complex/PPI

NADPH oxidase complex

Comment The induction of reactive oxygen species, as well as nitric oxide, from activated microglia can enhance the production of more potent free radicals such as peroxynitrite.
Formal Description
Interaction-ID: 7865

increases_quantity of

drug/chemical compound

Peroxynitrite

Comment The formation of peroxynitrite causes protein oxidation, lipid peroxidation and DNA damage, which ultimately lead to neuronal cell death.
Formal Description
Interaction-ID: 7866

drug/chemical compound

Peroxynitrite

increases_activity of

Comment The formation of peroxynitrite causes protein oxidation, lipid peroxidation and DNA damage, which ultimately lead to neuronal cell death.
Formal Description
Interaction-ID: 7867

drug/chemical compound

Peroxynitrite

increases_activity of

process

lipid peroxidation

Comment The formation of peroxynitrite causes protein oxidation, lipid peroxidation and DNA damage, which ultimately lead to neuronal cell death.
Formal Description
Interaction-ID: 7868

drug/chemical compound

Peroxynitrite

increases_activity of

Comment The formation of peroxynitrite causes protein oxidation, lipid peroxidation and DNA damage, which ultimately lead to neuronal cell death.
Formal Description
Interaction-ID: 7869

drug/chemical compound

Peroxynitrite

increases_activity of

process

cell death

in neurons
Comment Hypothesis: ROS and iNOS released through NADPH-dependent mechanisms contribute to the extensive oxidative damage found in the brains of AD patients.
Formal Description
Interaction-ID: 7932

none selected

Drugbank entries Show/Hide entries for or
Comment In both human AD brain tissue and fAbeta-treated cultured monocytes and primary microglia, there is a translocation of both the p47phox and p67phox subunits from the cytosol to the membrane.
Formal Description
Interaction-ID: 8326

gene/protein

NCF1

is localized in

cellular component

cytoplasm

and translocated to membrane
Comment In both human AD brain tissue and fAbeta-treated cultured monocytes and primary microglia, there is a translocation of both the p47phox and p67phox subunits from the cytosol to the membrane.
Formal Description
Interaction-ID: 8328

gene/protein

NCF2

is localized in

cellular component

cytoplasm

and translocated to membrane
Comment Fibrillar Abeta-stimulation also results in a relative increase in mRNA transcripts for both p47phox and gp91phox.
Formal Description
Interaction-ID: 8329

complex/PPI

Amyloid beta peptide (fibrillar)

increases_expression of

gene/protein

NCF1

Comment Fibrillar Abeta-stimulation also results in a relative increase in mRNA transcripts for both p47phox and gp91phox.
Formal Description
Interaction-ID: 8330

complex/PPI

Amyloid beta peptide (fibrillar)

increases_expression of

gene/protein

CYBB

Comment Astrocytes are the most abundant glial cell type in the brain.
Formal Description
Interaction-ID: 8331

tissue/cell line

astrocyte

is localized in

tissue/cell line

brain

Comment Reactive astrocytes are found adjacent to senile plaques.
Formal Description
Interaction-ID: 8332

tissue/cell line

astrocyte

interacts (colocalizes) with

Comment Plaque-associated astrocytes upregulate the expression of the chemokines MCP-1 and RANTES, which act as chemoattractants for microglia. Astrocytes also release the proinflammatory cytokines TNFalpha, IL1beta, as well as nitric oxide (NO).
Formal Description
Interaction-ID: 8333

tissue/cell line

astrocyte

increases_expression of

gene/protein

CCL2

Plaque-associated astrocytes upregulate the expression of the chemokines MCP-1 and RANTES.
Drugbank entries Show/Hide entries for CCL2
Comment Plaque-associated astrocytes upregulate the expression of the chemokines MCP-1 and RANTES, which act as chemoattractants for microglia. Astrocytes also release the proinflammatory cytokines TNFalpha, IL1beta, as well as nitric oxide (NO).
Formal Description
Interaction-ID: 8343

tissue/cell line

astrocyte

increases_expression of

gene/protein

CCL5

Plaque-associated astrocytes upregulate the expression of the chemokines MCP-1 and RANTES.
Drugbank entries Show/Hide entries for CCL5
Comment Plaque-associated astrocytes upregulate the expression of the chemokines MCP-1 and RANTES, which act as chemoattractants for microglia. Astrocytes also release the proinflammatory cytokines TNFalpha, IL1beta, as well as nitric oxide (NO).
Formal Description
Interaction-ID: 8344

tissue/cell line

astrocyte

affects_quantity of

gene/protein

TNF

Plaque-associated astrocytes upregulate the expression of the chemokines MCP-1 and RANTES.
Drugbank entries Show/Hide entries for TNF
Comment Plaque-associated astrocytes upregulate the expression of the chemokines MCP-1 and RANTES, which act as chemoattractants for microglia. Astrocytes also release the proinflammatory cytokines TNFalpha, IL1beta, as well as nitric oxide (NO).
Formal Description
Interaction-ID: 8346

tissue/cell line

astrocyte

affects_quantity of

gene/protein

IL1B

Plaque-associated astrocytes upregulate the expression of the chemokines MCP-1 and RANTES.
Drugbank entries Show/Hide entries for IL1B
Comment Confirmation of NADPH oxidase participation in Abeta-induced ROS production has been obtained utilizing cells obtained from patients with the rare recessive genetic disorder, chronic granulomatous disease (CGD). This disease is characterized by a mutation in the genes that encode one of the essential subunits of the NADPH oxidase: p22phox, p47phox, p67phox or gp91phox. These defects render the cells unable to generate H2 O2 in response to any agonist of the oxidase. Subsequent studies have substantiated that the NADPH oxidase is essential for Abeta-induced ROS production.
Formal Description
Interaction-ID: 8347

complex/PPI

NADPH oxidase complex

affects_quantity of

drug/chemical compound

Reactive oxygen species

if ROS production is Abeta-induced
Comment Confirmation of NADPH oxidase participation in Abeta-induced ROS production has been obtained utilizing cells obtained from patients with the rare recessive genetic disorder, chronic granulomatous disease (CGD). This disease is characterized by a mutation in the genes that encode one of the essential subunits of the NADPH oxidase: p22phox, p47phox, p67phox or gp91phox. These defects render the cells unable to generate H2 O2 in response to any agonist of the oxidase. Subsequent studies have substantiated that the NADPH oxidase is essential for Abeta-induced ROS production.
Formal Description
Interaction-ID: 8362

gene/protein mutant

CYBA-mut

increases_activity of

disease

Chronic granulomatous disease

Comment Confirmation of NADPH oxidase participation in Abeta-induced ROS production has been obtained utilizing cells obtained from patients with the rare recessive genetic disorder, chronic granulomatous disease (CGD). This disease is characterized by a mutation in the genes that encode one of the essential subunits of the NADPH oxidase: p22phox, p47phox, p67phox or gp91phox. These defects render the cells unable to generate H2 O2 in response to any agonist of the oxidase. Subsequent studies have substantiated that the NADPH oxidase is essential for Abeta-induced ROS production.
Formal Description
Interaction-ID: 8363

gene/protein mutant

NCF1-mut

increases_activity of

disease

Chronic granulomatous disease

Comment Confirmation of NADPH oxidase participation in Abeta-induced ROS production has been obtained utilizing cells obtained from patients with the rare recessive genetic disorder, chronic granulomatous disease (CGD). This disease is characterized by a mutation in the genes that encode one of the essential subunits of the NADPH oxidase: p22phox, p47phox, p67phox or gp91phox. These defects render the cells unable to generate H2 O2 in response to any agonist of the oxidase. Subsequent studies have substantiated that the NADPH oxidase is essential for Abeta-induced ROS production.
Formal Description
Interaction-ID: 8364

gene/protein mutant

NCF2-mut

increases_activity of

disease

Chronic granulomatous disease

Comment Confirmation of NADPH oxidase participation in Abeta-induced ROS production has been obtained utilizing cells obtained from patients with the rare recessive genetic disorder, chronic granulomatous disease (CGD). This disease is characterized by a mutation in the genes that encode one of the essential subunits of the NADPH oxidase: p22phox, p47phox, p67phox or gp91phox. These defects render the cells unable to generate H2 O2 in response to any agonist of the oxidase. Subsequent studies have substantiated that the NADPH oxidase is essential for Abeta-induced ROS production.
Formal Description
Interaction-ID: 8365

gene/protein mutant

CYBB-mut

increases_activity of

disease

Chronic granulomatous disease

Comment Confirmation of NADPH oxidase participation in Abeta-induced ROS production has been obtained utilizing cells obtained from patients with the rare recessive genetic disorder, chronic granulomatous disease (CGD). This disease is characterized by a mutation in the genes that encode one of the essential subunits of the NADPH oxidase: p22phox, p47phox, p67phox or gp91phox. These defects render the cells unable to generate H2 O2 in response to any agonist of the oxidase. Subsequent studies have substantiated that the NADPH oxidase is essential for Abeta-induced ROS production.
Formal Description
Interaction-ID: 8366

gene/protein mutant

CYBA-mut

decreases_quantity of

drug/chemical compound

H2O2

Comment Confirmation of NADPH oxidase participation in Abeta-induced ROS production has been obtained utilizing cells obtained from patients with the rare recessive genetic disorder, chronic granulomatous disease (CGD). This disease is characterized by a mutation in the genes that encode one of the essential subunits of the NADPH oxidase: p22phox, p47phox, p67phox or gp91phox. These defects render the cells unable to generate H2 O2 in response to any agonist of the oxidase. Subsequent studies have substantiated that the NADPH oxidase is essential for Abeta-induced ROS production.
Formal Description
Interaction-ID: 8367

gene/protein mutant

NCF1-mut

decreases_quantity of

drug/chemical compound

H2O2

Comment Confirmation of NADPH oxidase participation in Abeta-induced ROS production has been obtained utilizing cells obtained from patients with the rare recessive genetic disorder, chronic granulomatous disease (CGD). This disease is characterized by a mutation in the genes that encode one of the essential subunits of the NADPH oxidase: p22phox, p47phox, p67phox or gp91phox. These defects render the cells unable to generate H2 O2 in response to any agonist of the oxidase. Subsequent studies have substantiated that the NADPH oxidase is essential for Abeta-induced ROS production.
Formal Description
Interaction-ID: 8368

gene/protein mutant

NCF2-mut

decreases_quantity of

drug/chemical compound

H2O2

Comment Confirmation of NADPH oxidase participation in Abeta-induced ROS production has been obtained utilizing cells obtained from patients with the rare recessive genetic disorder, chronic granulomatous disease (CGD). This disease is characterized by a mutation in the genes that encode one of the essential subunits of the NADPH oxidase: p22phox, p47phox, p67phox or gp91phox. These defects render the cells unable to generate H2 O2 in response to any agonist of the oxidase. Subsequent studies have substantiated that the NADPH oxidase is essential for Abeta-induced ROS production.
Formal Description
Interaction-ID: 8369

gene/protein mutant

CYBB-mut

decreases_quantity of

drug/chemical compound

H2O2

Comment Levels of both dityrosine and nitrotyrosine are elevated in brain regions specifically affected in AD.
Formal Description
Interaction-ID: 8370

increases_quantity of

drug/chemical compound

Dityrosine

in brain regions specifically affected in AD
Comment Levels of both dityrosine and nitrotyrosine are elevated in brain regions specifically affected in AD.
Formal Description
Interaction-ID: 8381

increases_quantity of

drug/chemical compound

Nitrotyrosine

in brain regions specifically affected in AD
Comment Recent advances in proteomics have identified specific proteins which are nitrated in the AD brain including beta-actin, enolase, and L-lactate dehydrogenase.
Formal Description
Interaction-ID: 8383

affects_quantity of

protein modification

ACTB-nit

in AD brain
Comment Recent advances in proteomics have identified specific proteins which are nitrated in the AD brain including beta-actin, enolase, and L-lactate dehydrogenase.
Formal Description
Interaction-ID: 8393

affects_quantity of

protein modification

ENO1-nit

in AD brain
Comment Recent advances in proteomics have identified specific proteins which are nitrated in the AD brain including beta-actin, enolase, and L-lactate dehydrogenase.
Formal Description
Interaction-ID: 8412

affects_quantity of

protein modification

ENO2-nit

in AD brain
Comment Recent advances in proteomics have identified specific proteins which are nitrated in the AD brain including beta-actin, enolase, and L-lactate dehydrogenase.
Formal Description
Interaction-ID: 8414

affects_quantity of

complex/PPI

L-lactate dehydrogenase-nit

in AD brain
Comment The formation of peroxynitrite causes protein oxidation, lipid peroxidation and DNA damage, which ultimately lead to neuronal cell death.
Formal Description
Interaction-ID: 61043

drug/chemical compound

Peroxynitrite

increases_activity of

process

DNA damage

Comment In response to contact with fibrillar beta-amyloid, microglia secrete a diverse array of proinflammatory molecules.
Formal Description
Interaction-ID: 80161

increases_activity of

Comment In response to contact with fibrillar beta-amyloid, microglia secrete a diverse array of proinflammatory molecules.
Formal Description
Interaction-ID: 80162

increases_activity of

tissue/cell line

microglia

Comment In response to contact with fibrillar beta-amyloid, microglia secrete a diverse array of proinflammatory molecules.
Formal Description
Interaction-ID: 80163

increases_activity of

Comment The source of fibrillar beta-amyloid induced reactive oxygen species is primarily the microglial nicotinamide adenine dinucleotide phosphate (NADPH) oxidase.
Formal Description
Interaction-ID: 80164

increases_quantity of

drug/chemical compound

Reactive oxygen species

Comment The source of fibrillar beta-amyloid induced reactive oxygen species is primarily the microglial nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. The NADPH oxidase is a multicomponent enzyme complex that, upon activation, produces the highly reactive free radical superoxide.
Formal Description
Interaction-ID: 80165

increases_activity of

complex/PPI

NADPH oxidase complex

Comment Fibrillar Abeta-stimulation also results in a relative increase in mRNA transcripts for both p47phox and gp91phox.
Formal Description
Interaction-ID: 80166

increases_expression of

gene/protein

NCF1

Comment Fibrillar Abeta-stimulation also results in a relative increase in mRNA transcripts for both p47phox and gp91phox.
Formal Description
Interaction-ID: 80167

increases_expression of

gene/protein

CYBB

Comment The principal neuropathological hallmarks of Alzheimer's disease are the senile plaques and the neurofibrillary tangles.
Formal Description
Interaction-ID: 80168

increases_activity of