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Field	Query

	Field	Term

General Information:

Id:	1,184
Diseases:	Alzheimer disease - [OMIM] Chronic granulomatous disease
Organism:	Mammalia
Publication type:	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 disease Alzheimer disease

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	phenotype amyloid beta deposits 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	process microglial cell activation increases_activity of process inflammatory response within the diseased brain

Comment	Microglia are the resident innate immune cells in the brain.
Formal Description Interaction-ID: 7855	tissue/cell line microglia increases_activity of process innate immune response in brain; they are the resident innate immune cells

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 process innate immune response

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 process inflammatory response

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	disease Alzheimer disease 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	disease Alzheimer disease increases_quantity of phenotype amyloid beta deposits

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	process microglial cell activation 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 process protein oxidation

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 process cellular response to DNA damage stimulus

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	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 phenotype amyloid beta deposits concerning reactive astrocytes

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	gene/protein CCL2 is_expressed_in tissue/cell line astrocyte Plaque-associated astrocytes upregulate the expression of the chemokines MCP-1 and RANTES.
Drugbank entries	Show/Hide entries for CCL2
Drugbank DB01055	Mimosine inhibitor CCL2
Drugbank DB01406	Danazol inhibitor CCL2
Drugbank DB01055	Mimosine inhibitor 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	gene/protein CCL5 is_expressed_in tissue/cell line astrocyte Plaque-associated astrocytes upregulate the expression of the chemokines MCP-1 and RANTES.
Drugbank entries	Show/Hide entries for CCL5
Drugbank DB02322	Heparin Disaccharide I-S not specified CCL5
Drugbank DB02353	Heparin Disaccharide Iii-S not specified CCL5
Drugbank DB02322	Heparin Disaccharide I-S not specified CCL5
Drugbank DB02353	Heparin Disaccharide Iii-S not specified 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
Drugbank DB00005	Etanercept antibody TNF
Drugbank DB00051	Adalimumab antibody TNF
Drugbank DB00065	Infliximab inhibitor TNF
Drugbank DB00608	Chloroquine not specified TNF
Drugbank DB01041	Thalidomide inhibitor TNF
Drugbank DB01296	Glucosamine not specified TNF
Drugbank DB01407	Clenbuterol other/unknown TNF
Drugbank DB01411	Pranlukast other/unknown TNF
Drugbank DB01427	Amrinone inhibitor TNF
Drugbank DB00051	Adalimumab antibody TNF
Drugbank DB00065	Infliximab inhibitor TNF
Drugbank DB01427	Amrinone inhibitor 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
Drugbank DB01017	Minocycline modulator IL1B
Drugbank DB05260	Gallium nitrate antagonist IL1B
Drugbank DB06168	Canakinumab not specified IL1B
Drugbank DB06168	Canakinumab not specified 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	disease Alzheimer disease 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	disease Alzheimer disease 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	disease Alzheimer disease 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	disease Alzheimer disease 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	disease Alzheimer disease 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	disease Alzheimer disease 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

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