CIDeRplusGeneral Information:
| Id: | 1,377 |
| Diseases: |
Alzheimer disease
- [OMIM]
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| 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. |
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Formal Description Interaction-ID: 9447 |
gene/protein increases_activity of process |
| 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. |
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Formal Description Interaction-ID: 9448 |
process increases_quantity of gene/protein |
| 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. |
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Formal Description Interaction-ID: 9449 |
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| 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. |
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Formal Description Interaction-ID: 9450 |
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| 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. |
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Formal Description Interaction-ID: 9451 |
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| 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. |
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Formal Description Interaction-ID: 9452 |
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| 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. |
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Formal Description Interaction-ID: 9453 |
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| 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. |
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Formal Description Interaction-ID: 9454 |
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| 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. |
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Formal Description Interaction-ID: 9455 |
disease 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. |
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Formal Description Interaction-ID: 9456 |
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| 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. |
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Formal Description Interaction-ID: 9457 |
phenotype increases_activity of disease |
| 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. |
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Formal Description Interaction-ID: 9458 |
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| 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. |
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Formal Description Interaction-ID: 9459 |
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| 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. |
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Formal Description Interaction-ID: 9460 |
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| Comment | OS (oxidative stress) results from several cellular insults such as aging, hyperglycemia, hypoxic insults that are all well known risk factors for AD development. |
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Formal Description Interaction-ID: 9461 |
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| Comment | OS (oxidative stress) results from several cellular insults such as aging, hyperglycemia, hypoxic insults that are all well known risk factors for AD development. |
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Formal Description Interaction-ID: 9462 |
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| Comment | OS (oxidative stress) results from several cellular insults such as aging, hyperglycemia, hypoxic insults that are all well known risk factors for AD development. |
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Formal Description Interaction-ID: 9463 |
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| 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. |
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Formal Description Interaction-ID: 9476 |
gene/protein increases_quantity of drug/chemical compound 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. |
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Formal Description Interaction-ID: 9526 |
drug/chemical compound Dityrosine increases_quantity of phenotype |
| 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. |
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Formal Description Interaction-ID: 9527 |
drug/chemical compound Reactive oxygen species increases_quantity of gene/protein |
| Comment | Abeta accumulation and plaques cooccurs with the common sporadic form of AD. |
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Formal Description Interaction-ID: 9528 |
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| Comment | Toxic forms of aggregated Abeta peptides favor Ca2+ influx into neurons by inducing membrane-associated OS, rendering neurons vulnerable to excitotoxicity and apoptosis. |
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Formal Description Interaction-ID: 9529 |
phenotype affects_activity of process |
| 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. |
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Formal Description Interaction-ID: 9533 |
phenotype affects_activity of process |
| 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. |
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Formal Description Interaction-ID: 9550 |
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| Comment | The increased expression of BACE1 induced by OS is regulated by the gamma-secretase. |
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Formal Description Interaction-ID: 9551 |
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| 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. |
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Formal Description Interaction-ID: 9552 |
complex/PPI Gamma-secretase complex increases_expression of gene/protein |
| 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. |
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Formal Description Interaction-ID: 9635 |
process increases_activity of phenotype |
| Comment | Mitochondrial mutations accumulate during brain aging and neurodegenerative diseases. Mutations in mitochondrial DNA cause a respiratory chain dysfunction, which can increase cellular OS. |
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Formal Description Interaction-ID: 9643 |
phenotype increases_activity of phenotype |
| Comment | Mitochondrial mutations accumulate during brain aging and neurodegenerative diseases. Mutations in mitochondrial DNA cause a respiratory chain dysfunction, which can increase cellular OS. |
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Formal Description Interaction-ID: 9645 |
phenotype increases_activity of phenotype |
| Comment | Hypoxia significantly up-regulates BACE1 gene expression, resulting in increased beta-secretase activity. |
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Formal Description Interaction-ID: 9706 |
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| Drugbank entries | Show/Hide entries for BACE1 |
| Comment | Hypoxia significantly up-regulates BACE1 gene expression, resulting in increased beta-secretase activity. |
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Formal Description Interaction-ID: 9707 |
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| 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. |
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Formal Description Interaction-ID: 9708 |
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| Comment | Hypoxia increases Abeta deposition and neuritic plaque formation, as well as memory deficits, providing a molecular mechanistic link of vascular factors with AD. |
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Formal Description Interaction-ID: 9709 |
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| Comment | The hypoxia inducible factor (HIF)-1alpha, a molecule that regulates oxygen homeostasis binds to the BACE1 promoter. |
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Formal Description Interaction-ID: 9710 |
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| Drugbank entries | Show/Hide entries for HIF1A |
| Comment | Overexpression of HIF-1alpha in neuronal cells increases BACE1 mRNA and protein levels. |
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Formal Description Interaction-ID: 9740 |
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| 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. |
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Formal Description Interaction-ID: 9748 |
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| 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. |
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Formal Description Interaction-ID: 9750 |
gene/protein interacts (colocalizes) with gene/protein |
| 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. |
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Formal Description Interaction-ID: 9751 |
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| Drugbank entries | Show/Hide entries for HIF1A |
| Comment | Hypoxia increases ROS via the mitochondrial transport chain and specifically by the function of complex III. |
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Formal Description Interaction-ID: 9773 |
process increases_quantity of drug/chemical compound Reactive oxygen species |