General Information:

Id: 1,377
Diseases: Alzheimer disease - [OMIM]
Mammalia
review
Reference: Guglielmotto M et al.(2010) Oxidative stress mediates the pathogenic effect of different Alzheimers disease risk factors Front Aging Neurosci 2: 3 [PMID: 20552043]

Interaction Information:

Comment Oxidative stress (OS) and amyloid beta peptide (Abeta) are linked to each other since Abeta aggregation induces OS in vivo and in vitro, and oxidant agents increase the production of Abeta.
Formal Description
Interaction-ID: 9447

gene/protein

Amyloid beta peptide

increases_activity of

via Abeta aggregation
Comment Oxidative stress (OS) and amyloid beta peptide (Abeta) are linked to each other since Abeta aggregation induces OS in vivo and in vitro, and oxidant agents increase the production of Abeta.
Formal Description
Interaction-ID: 9448

increases_quantity of

gene/protein

Amyloid beta peptide

as oxidant agents increase the production of Abeta
Comment Oxidative stress (OS) and amyloid beta peptide (Abeta) are linked to each other since Abeta aggregation induces OS in vivo and in vitro, and oxidant agents increase the production of Abeta.
Formal Description
Interaction-ID: 9449

drug/chemical compound

Oxidizing agent

increases_quantity of

gene/protein

Amyloid beta peptide

Comment Oxidative stress (OS) and amyloid beta peptide (Abeta) are linked to each other since Abeta aggregation induces OS in vivo and in vitro, and oxidant agents increase the production of Abeta.
Formal Description
Interaction-ID: 9450

gene/protein

Amyloid beta peptide

increases_quantity of

Comment Oxidative stress (OS) and amyloid beta peptide (Abeta) are linked to each other since Abeta aggregation induces OS in vivo and in vitro, and oxidant agents increase the production of Abeta.
Formal Description
Interaction-ID: 9451

increases_quantity of

drug/chemical compound

Oxidizing agent

Comment The expression and activity of beta-secretase (named BACE1; beta-site APP cleaving enzyme) is increased by oxidant agents and by lipid peroxidation product 4-hydroxynonenal.
Formal Description
Interaction-ID: 9452

drug/chemical compound

Oxidizing agent

increases_expression of

gene/protein

BACE1

Drugbank entries Show/Hide entries for BACE1
Comment The expression and activity of beta-secretase (named BACE1; beta-site APP cleaving enzyme) is increased by oxidant agents and by lipid peroxidation product 4-hydroxynonenal.
Formal Description
Interaction-ID: 9453

process

lipid oxidation

increases_expression of

gene/protein

BACE1

Drugbank entries Show/Hide entries for BACE1
Comment The expression and activity of beta-secretase (named BACE1; beta-site APP cleaving enzyme) is increased by oxidant agents and by lipid peroxidation product 4-hydroxynonenal.
Formal Description
Interaction-ID: 9454

process

lipid oxidation

increases_quantity of

drug/chemical compound

4-Hydroxy-2,3-nonenal

Comment Post mortem analysis of the brains of AD patients found increased levels of lipid peroxidation in brain regions that are affected by an early neurodegeneration.
Formal Description
Interaction-ID: 9455

increases_activity of

process

lipid peroxidation

affected by neurodegeneration
Comment Post mortem analysis of the brains of AD patients found increased levels of lipid peroxidation in brain regions that are affected by an early neurodegeneration.
Formal Description
Interaction-ID: 9456

phenotype

neurodegeneration

increases_activity of

process

lipid peroxidation

Comment Post mortem analysis of the brains of AD patients found increased levels of lipid peroxidation in brain regions that are affected by an early neurodegeneration.
Formal Description
Interaction-ID: 9457

phenotype

neurodegeneration

increases_activity of

found in post mortem brain
Comment Several studies have shown that protein oxidation also increases exponentially with brain aging and is associated with a decreased capacity of the antioxidative defense machinery.
Formal Description
Interaction-ID: 9458

process

aging

increases_activity of

Comment Several studies have shown that protein oxidation also increases exponentially with brain aging and is associated with a decreased capacity of the antioxidative defense machinery.
Formal Description
Interaction-ID: 9459

process

aging

decreases_activity of

Comment AD is classified into two forms: sporadic AD, which is correlated to aging, and a rare familial earlyonset AD (FAD), caused by gene mutations.
Formal Description
Interaction-ID: 9460

process

aging

increases_activity of

Comment OS results from several cellular insults such as aging, hyperglycemia, hypoxic insults that are all well known risk factors for AD development.
Formal Description
Interaction-ID: 9461

process

aging

increases_activity of

Comment OS results from several cellular insults such as aging, hyperglycemia, hypoxic insults that are all well known risk factors for AD development.
Formal Description
Interaction-ID: 9462

phenotype

hyperglycemia

increases_activity of

Comment OS results from several cellular insults such as aging, hyperglycemia, hypoxic insults that are all well known risk factors for AD development.
Formal Description
Interaction-ID: 9463

phenotype

hypoxia

increases_activity of

Comment It has been found that the phenoxy radical of Abeta Tyr-10 produced by the reaction with ROS causes neurotoxicity and results in the formation of dityrosines which, in turn, accelerate the aggregation of Abeta peptides.
Formal Description
Interaction-ID: 9476

increases_quantity of

drug/chemical compound

Dityrosine

50607 [ChEBI] dityrosine
Comment It has been found that the phenoxy radical of Abeta Tyr-10 produced by the reaction with ROS causes neurotoxicity and results in the formation of dityrosines which, in turn, accelerate the aggregation of Abeta peptides.
Formal Description
Interaction-ID: 9526

drug/chemical compound

Dityrosine

increases_quantity of

50607 [ChEBI] dityrosine
Comment It has been found that the phenoxy radical of Abeta Tyr-10 produced by the reaction with ROS causes neurotoxicity and results in the formation of dityrosines which, in turn, accelerate the aggregation of Abeta peptides.
Formal Description
Interaction-ID: 9527

drug/chemical compound

Reactive oxygen species

increases_quantity of

Comment Abeta accumulation and plaques cooccurs with the common sporadic form of AD.
Formal Description
Interaction-ID: 9528

increases_quantity of

Comment Toxic forms of aggregated Abeta peptides favor Ca2+ influx into neurons by inducing membrane-associated OS, rendering neurons vulnerable to excitotoxicity and apoptosis.
Formal Description
Interaction-ID: 9529

affects_activity of

Toxic forms of aggregated Abeta peptides favor Ca2+ influx into neurons.
Comment Toxic forms of aggregated Abeta peptides favor Ca2+ influx into neurons by inducing membrane-associated OS (may be an early event in progression from normal aging to AD pathology), rendering neurons vulnerable to excitotoxicity and apoptosis.
Formal Description
Interaction-ID: 9533

affects_activity of

Toxic forms of aggregated Abeta peptides favor Ca2+ influx into neurons by inducing membrane-associated OS (oxidative stress).
Comment Hypothesis: Small soluble aggregates of Abeta, including protofibrils and oligomers, may be more toxic than Abeta fibrils. These data may help explain why neurodegeneration and specific spatial learning deficits may occur in AD animal models before the appearance of amyloid plaques.
Formal Description
Interaction-ID: 9540

none selected

Drugbank entries Show/Hide entries for or
Comment OS increases the gamma-secretase activity. OS is the only known factor able to augment the gamma-secretase cleavage by increasing the expression of PS1, the catalytic subunit of the endoprotease.
Formal Description
Interaction-ID: 9550

increases_activity of

Comment The increased expression of BACE1 induced by OS is regulated by the gamma-secretase.
Formal Description
Interaction-ID: 9551

increases_expression of

gene/protein

BACE1

Drugbank entries Show/Hide entries for BACE1
Comment The increased expression of BACE1 induced by OS is regulated by the gamma-secretase. There is a positive feedback loop in which increased gamma-secretase activity results in up-regulation of BACE1 expression.
Formal Description
Interaction-ID: 9552

increases_expression of

gene/protein

BACE1

in a positive feedback loop
Drugbank entries Show/Hide entries for BACE1
Comment Mitochondrial mutations accumulate during brain aging and neurodegenerative diseases. Mutations in mitochondrial DNA cause a respiratory chain dysfunction, which can increase cellular OS.
Formal Description
Interaction-ID: 9635

process

aging

increases_activity of

brain aging increases mitochondrial mutations
Comment Mitochondrial mutations accumulate during brain aging and neurodegenerative diseases. Mutations in mitochondrial DNA cause a respiratory chain dysfunction, which can increase cellular OS.
Formal Description
Interaction-ID: 9643

phenotype

neurodegeneration

increases_activity of

neurodegenerative diseases increase mitochondrial mutations
Comment Mitochondrial mutations accumulate during brain aging and neurodegenerative diseases. Mutations in mitochondrial DNA cause a respiratory chain dysfunction, which can increase cellular OS.
Formal Description
Interaction-ID: 9645

increases_activity of

Mutations in mitochondrial DNA cause a respiratory chain dysfunction.
Comment Hypoxia significantly up-regulates BACE1 gene expression, resulting in increased beta-secretase activity.
Formal Description
Interaction-ID: 9706

phenotype

hypoxia

increases_expression of

gene/protein

BACE1

Drugbank entries Show/Hide entries for BACE1
Comment Hypoxia significantly up-regulates BACE1 gene expression, resulting in increased beta-secretase activity.
Formal Description
Interaction-ID: 9707

phenotype

hypoxia

increases_activity of

gene/protein

BACE1

Drugbank entries Show/Hide entries for BACE1
Comment Hypoxia increases Abeta deposition and neuritic plaque formation, as well as memory deficits, providing a molecular mechanistic link of vascular factors with AD.
Formal Description
Interaction-ID: 9708

phenotype

hypoxia

increases_quantity of

Comment Hypoxia increases Abeta deposition and neuritic plaque formation, as well as memory deficits, providing a molecular mechanistic link of vascular factors with AD.
Formal Description
Interaction-ID: 9709

phenotype

hypoxia

affects_activity of

Comment The hypoxia inducible factor (HIF)-1alpha, a molecule that regulates oxygen homeostasis binds to the BACE1 promoter.
Formal Description
Interaction-ID: 9710

gene/protein

HIF1A

interacts (colocalizes) with

gene/protein

BACE1 (promoter)

Drugbank entries Show/Hide entries for HIF1A
Comment Overexpression of HIF-1alpha in neuronal cells increases BACE1 mRNA and protein levels.
Formal Description
Interaction-ID: 9740

gene/protein

HIF1A

increases_expression of

gene/protein

BACE1

in neuronal cells; if HIF1A is overexpressed, via binding to BACE1 promoter;
Drugbank entries Show/Hide entries for HIF1A or BACE1
Comment Hypoxia was also found to increase gamma-secretase activity: HIF-1alpha binds to the promoter of anterior pharynx-defective phenotype (APH-1), a key component of the gamma-secretase complex, to up-regulate its expression.
Formal Description
Interaction-ID: 9748

phenotype

hypoxia

increases_activity of

Comment Hypoxia was also found to increase gamma-secretase activity: HIF-1alpha binds to the promoter of anterior pharynx-defective phenotype (APH-1), a key component of the gamma-secretase complex, to up-regulate its expression.
Formal Description
Interaction-ID: 9750

gene/protein

HIF1A

interacts (colocalizes) with

gene/protein

APH1A (promoter)

HIF-1alpha binds to the promoter of anterior pharynx-defective phenotype (APH-1).
Drugbank entries Show/Hide entries for HIF1A
Comment Hypoxia was also found to increase gamma-secretase activity: HIF-1alpha binds to the promoter of anterior pharynx-defective phenotype (APH-1), a key component of the gamma-secretase complex, to up-regulate its expression.
Formal Description
Interaction-ID: 9751

gene/protein

HIF1A

increases_expression of

gene/protein

APH1A

Drugbank entries Show/Hide entries for HIF1A
Comment Hypoxia increases ROS via the mitochondrial transport chain and specifically by the function of complex III.
Formal Description
Interaction-ID: 9773

phenotype

hypoxia

increases_quantity of

drug/chemical compound

Reactive oxygen species

via the mitochondrial transport chain, specifically by the function of complex III