CIDeRplusGeneral Information:
| Id: | 1,107 |
| Diseases: |
Alzheimer disease
- [OMIM]
Dementia |
| Mammalia | |
| review | |
| Reference: | Candore G et al.(2010) Inflammation, cytokines, immune response, apolipoprotein E, cholesterol, and oxidative stress in Alzheimer disease: therapeutic implications Rejuvenation Res 13: 301-313 [PMID: 20462385] |
Interaction Information:
| Comment | Senile plaques (characterized by the accumulation of proteinsin the form of beta-pleated sheet fibrils, which are composed mainly of a 42-amino-acid peptide known as beta-amyloid (Ab), and neurofibrillary tangles, mainly composed by a cytoskeletal hyperphosphorylated protein tau) in AD brains are associated with reactive astrocytes and activated microglial cells, which overexpress cytokines and acute-phase proteins. |
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Formal Description Interaction-ID: 7074 |
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| Comment | Senile plaques (characterized by the accumulation of proteinsin the form of beta-pleated sheet fibrils, which are composed mainly of a 42-amino-acid peptide known as beta-amyloid (Ab), and neurofibrillary tangles, mainly composed by a cytoskeletal hyperphosphorylated protein tau) in AD brains are associated with reactive astrocytes and activated microglial cells, which overexpress cytokines and acute-phase proteins. |
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Formal Description Interaction-ID: 7079 |
phenotype affects_activity of phenotype |
| Comment | Senile plaques (characterized by the accumulation of proteinsin the form of beta-pleated sheet fibrils, which are composed mainly of a 42-amino-acid peptide known as beta-amyloid (Ab),and neurofibrillary tangles, mainly composed by a cytoskeletal hyperphosphorylated protein tau) in AD brains are associated with reactive astrocytes and activated microglial cells, which overexpress cytokines and acute-phase proteins. |
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Formal Description Interaction-ID: 7080 |
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| Comment | Microglial activation can be due to local or systemic inflammation. |
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Formal Description Interaction-ID: 7094 |
process increases_activity of tissue/cell line |
| Comment | Cytokines are critical in the pathophysiology of AD. |
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Formal Description Interaction-ID: 7122 |
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| Comment | In transgenic AD-prone mice, overexpression of TGF-beta reduced plaque burden. |
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Formal Description Interaction-ID: 7123 |
gene/protein decreases_quantity of phenotype |
| Drugbank entries | Show/Hide entries for TGFB1 |
| Comment | The APOE4 allele is a genetic variant that has been clearly associated with increased risk of late-onset AD. |
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Formal Description Interaction-ID: 7243 |
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| Comment | The APO-epsilon4 allele accelerates amyloid deposition and promotes Abeta aggregation in cholesterol-rich lipid rafts, enhancing aggregation into senile plaques. |
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Formal Description Interaction-ID: 7344 |
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| Comment | High cholesterol levels at midlife are a considerable risk factor for dementia/AD in most of longterm follow-up studies. |
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Formal Description Interaction-ID: 7346 |
phenotype increases_activity of disease |
| Comment | High cholesterol levels at midlife are a considerable risk factor for dementia/AD in most of longterm follow-up studies. |
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Formal Description Interaction-ID: 7348 |
phenotype increases_activity of disease Dementia |
| Comment | Increased cholesterol leads to increased cleavage of APP and increased Abeta production. |
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Formal Description Interaction-ID: 7349 |
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| Drugbank entries | Show/Hide entries for APP |
| Comment | Increased cholesterol leads to increased cleavage of APP and increased Abeta production. |
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Formal Description Interaction-ID: 7350 |
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| Comment | Reduction of cellular cholesterol decreases the gamma-secretase activity, which is responsible for Abeta generation. |
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Formal Description Interaction-ID: 7351 |
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| Comment | Reduction of cellular cholesterol decreases the gamma-secretase activity, which is responsible for Abeta generation. |
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Formal Description Interaction-ID: 7355 |
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| Comment | Cortical and hippocampal oxidative stress is a very early event in the pathophysiology of sporadic AD and correlates with the development of specific cognitive deficits. |
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Formal Description Interaction-ID: 7514 |
process affects_activity of disease |
| Comment | The HO-1 gene is redox regulated, and its activation represents a protective system potentially active against brain oxidative injury. Its expression in AD patients brain is significantly increased, and the spatial distribution of HO-1 expression in diseased brain is essentially identical to that of pathological expression of tau. |
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Formal Description Interaction-ID: 7525 |
gene/protein affects_activity of disease |
| Drugbank entries | Show/Hide entries for HMOX1 |
| Comment | HO-1 immunoreactivity is greatly increased in neurons and astrocytes of the hippocampus and cerebral cortex of individuals with AD and colocalizes in senile plaques and neurofibrillary tangles. |
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Formal Description Interaction-ID: 7533 |
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| Drugbank entries | Show/Hide entries for HMOX1 |
| Comment | Activation of HO-1 in neurons is strongly protective against oxidative damage and cell death. |
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Formal Description Interaction-ID: 7535 |
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| Drugbank entries | Show/Hide entries for HMOX1 |
| Comment | Curcumin is a polyphenolic substance that has the potential to inhibit lipid peroxidation and to effectively intercept and neutralize ROS (superoxide, peroxyl, hydroxyl radicals) and nitric oxide (NO)-based free radicals (nitric oxide and peroxynitrite). |
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Formal Description Interaction-ID: 7571 |
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| Comment | Curcumin is a polyphenolic substance that has the potential to inhibit lipid peroxidation and to effectively intercept and neutralize ROS (superoxide, peroxyl, hydroxyl radicals) and nitric oxide (NO)-based free radicals (nitric oxide and peroxynitrite). |
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Formal Description Interaction-ID: 7574 |
drug/chemical compound decreases_activity of drug/chemical compound Reactive oxygen species |
| Comment | Of particular interest is the ability of curcumin to inhibit cyclooxygenase enzymes and to reduce the activation of nuclear transcription factor NF-kappaB. |
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Formal Description Interaction-ID: 7577 |
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| Comment | Of particular interest is the ability of curcumin to inhibit cyclooxygenase enzymes and to reduce the activation of nuclear transcription factor NF-kappaB. |
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Formal Description Interaction-ID: 7579 |
drug/chemical compound decreases_activity of complex/PPI NF-kappaB complex |
| Comment | Plant-derived phenolic agents with analogous chemical structures to curcumin have also been demonstrated to strongly activate HO-1 expression and to defend cells against oxidative stress, in particular carnosol, zerumbone, resveratrol, rosolic acid, and sulforaphanes. |
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Formal Description Interaction-ID: 7580 |
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| Drugbank entries | Show/Hide entries for HMOX1 |
| Comment | Plant-derived phenolic agents with analogous chemical structures to curcumin have also been demonstrated to strongly activate HO-1 expression and to defend cells against oxidative stress, in particular carnosol, zerumbone, resveratrol, rosolic acid, and sulforaphanes. |
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Formal Description Interaction-ID: 7581 |
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| Comment | Plant-derived phenolic agents with analogous chemical structures to curcumin have also been demonstrated to strongly activate HO-1 expression and to defend cells against oxidative stress, in particular carnosol, zerumbone, resveratrol, rosolic acid, and sulforaphanes. |
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Formal Description Interaction-ID: 7582 |
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| Drugbank entries | Show/Hide entries for HMOX1 |
| Comment | Plant-derived phenolic agents with analogous chemical structures to curcumin have also been demonstrated to strongly activate HO-1 expression and to defend cells against oxidative stress, in particular carnosol, zerumbone, resveratrol, rosolic acid, and sulforaphanes. |
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Formal Description Interaction-ID: 7583 |
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| Comment | Plant-derived phenolic agents with analogous chemical structures to curcumin have also been demonstrated to strongly activate HO-1 expression and to defend cells against oxidative stress, in particular carnosol, zerumbone, resveratrol, rosolic acid, and sulforaphanes. |
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Formal Description Interaction-ID: 7584 |
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| Drugbank entries | Show/Hide entries for Resveratrol or HMOX1 |
| Comment | Plant-derived phenolic agents with analogous chemical structures to curcumin have also been demonstrated to strongly activate HO-1 expression and to defend cells against oxidative stress, in particular carnosol, zerumbone, resveratrol, rosolic acid, and sulforaphanes. |
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Formal Description Interaction-ID: 7585 |
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| Drugbank entries | Show/Hide entries for Resveratrol |
| Comment | Plant-derived phenolic agents with analogous chemical structures to curcumin have also been demonstrated to strongly activate HO-1 expression and to defend cells against oxidative stress, in particular carnosol, zerumbone, resveratrol, rosolic acid, and sulforaphanes. |
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Formal Description Interaction-ID: 7586 |
drug/chemical compound Rosolic acid increases_expression of gene/protein |
| Drugbank entries | Show/Hide entries for HMOX1 |
| Comment | Plant-derived phenolic agents with analogous chemical structures to curcumin have also been demonstrated to strongly activate HO-1 expression and to defend cells against oxidative stress, in particular carnosol, zerumbone, resveratrol, rosolic acid, and sulforaphanes. |
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Formal Description Interaction-ID: 7587 |
drug/chemical compound Rosolic acid affects_activity of process |
| Comment | Plant-derived phenolic agents with analogous chemical structures to curcumin have also been demonstrated to strongly activate HO-1 expression and to defend cells against oxidative stress, in particular carnosol, zerumbone, resveratrol, rosolic acid, and sulforaphanes. |
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Formal Description Interaction-ID: 7588 |
drug/chemical compound Sulforaphane increases_expression of gene/protein |
| Drugbank entries | Show/Hide entries for HMOX1 |
| Comment | Plant-derived phenolic agents with analogous chemical structures to curcumin have also been demonstrated to strongly activate HO-1 expression and to defend cells against oxidative stress, in particular carnosol, zerumbone, resveratrol, rosolic acid, and sulforaphanes. |
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Formal Description Interaction-ID: 7589 |
drug/chemical compound Sulforaphane affects_activity of process |
| Comment | Activation of HO-1 in neurons is strongly protective against oxidative damage and cell death. |
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Formal Description Interaction-ID: 20816 |
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| Drugbank entries | Show/Hide entries for HMOX1 |
| Comment | Plant-derived phenolic agents with analogous chemical structures to curcumin have also been demonstrated to strongly activate HO-1 expression and to defend cells against oxidative stress, in particular carnosol, zerumbone, resveratrol, rosolic acid, and sulforaphanes. |
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Formal Description Interaction-ID: 20818 |
drug/chemical compound Rosolic acid decreases_activity of process |
| Comment | Plant-derived phenolic agents with analogous chemical structures to curcumin have also been demonstrated to strongly activate HO-1 expression and to defend cells against oxidative stress, in particular carnosol, zerumbone, resveratrol, rosolic acid, and sulforaphanes. |
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Formal Description Interaction-ID: 20819 |
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| Drugbank entries | Show/Hide entries for Resveratrol |
| Comment | Plant-derived phenolic agents with analogous chemical structures to curcumin have also been demonstrated to strongly activate HO-1 expression and to defend cells against oxidative stress, in particular carnosol, zerumbone, resveratrol, rosolic acid, and sulforaphanes. |
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Formal Description Interaction-ID: 20820 |
|
| Comment | Plant-derived phenolic agents with analogous chemical structures to curcumin have also been demonstrated to strongly activate HO-1 expression and to defend cells against oxidative stress, in particular carnosol, zerumbone, resveratrol, rosolic acid, and sulforaphanes. |
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Formal Description Interaction-ID: 20821 |
drug/chemical compound Sulforaphane decreases_activity of process |
| Comment | Plant-derived phenolic agents with analogous chemical structures to curcumin have also been demonstrated to strongly activate HO-1 expression and to defend cells against oxidative stress, in particular carnosol, zerumbone, resveratrol, rosolic acid, and sulforaphanes. |
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Formal Description Interaction-ID: 20822 |
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| Comment | In transgenic AD-prone mice, overexpression of TGF-beta reduced plaque burden. |
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Formal Description Interaction-ID: 79061 |
gene/protein increases_activity of process |
| Drugbank entries | Show/Hide entries for TGFB1 |
| Comment | Reduction of cellular cholesterol decreases the gamma-secretase activity, which is responsible for Abeta generation. |
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Formal Description Interaction-ID: 80460 |
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| Drugbank entries | Show/Hide entries for Cholesterol |
| Comment | Increased cholesterol leads to increased cleavage of APP and increased Abeta production. |
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Formal Description Interaction-ID: 82834 |
phenotype decreases_quantity of gene/protein |
| Drugbank entries | Show/Hide entries for APP |
| Comment | Of particular interest is the ability of curcumin to inhibit cyclooxygenase enzymes and to reduce the activation of nuclear transcription factor NF-kappaB. |
|
Formal Description Interaction-ID: 106878 |
drug/chemical compound decreases_activity of complex/PPI NF-kappaB complex |
| Comment | Senile plaques (characterized by the accumulation of proteinsin the form of beta-pleated sheet fibrils, which are composed mainly of a 42-amino-acid peptide known as beta-amyloid (Ab),and neurofibrillary tangles, mainly composed by a cytoskeletal hyperphosphorylated protein tau) in AD brains are associated with reactive astrocytes and activated microglial cells, which overexpress cytokines and acute-phase proteins. |
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Formal Description Interaction-ID: 145266 |
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| Comment | Senile plaques (characterized by the accumulation of proteinsin the form of beta-pleated sheet fibrils, which are composed mainly of a 42-amino-acid peptide known as beta-amyloid (Ab), and neurofibrillary tangles, mainly composed by a cytoskeletal hyperphosphorylated protein tau) in AD brains are associated with reactive astrocytes and activated microglial cells, which overexpress cytokines and acute-phase proteins. |
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Formal Description Interaction-ID: 145267 |
phenotype affects_activity of phenotype |
| Comment | Senile plaques (characterized by the accumulation of proteinsin the form of beta-pleated sheet fibrils, which are composed mainly of a 42-amino-acid peptide known as beta-amyloid (Ab),and neurofibrillary tangles, mainly composed by a cytoskeletal hyperphosphorylated protein tau) in AD brains are associated with reactive astrocytes and activated microglial cells, which overexpress cytokines and acute-phase proteins. |
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Formal Description Interaction-ID: 145268 |
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| Comment | High cholesterol levels at midlife are a considerable risk factor for dementia/AD in most of longterm follow-up studies. |
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Formal Description Interaction-ID: 150123 |
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| Comment | Increased cholesterol leads to increased cleavage of APP and increased Abeta production. |
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Formal Description Interaction-ID: 150124 |
phenotype increases_quantity of gene/protein |
| Comment | High cholesterol levels at midlife are a considerable risk factor for dementia/AD in most of longterm follow-up studies. |
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Formal Description Interaction-ID: 150126 |
phenotype increases_activity of phenotype |
| Comment | Senile plaques (characterized by the accumulation of proteinsin the form of beta-pleated sheet fibrils, which are composed mainly of a 42-amino-acid peptide known as beta-amyloid (Ab), and neurofibrillary tangles, mainly composed by a cytoskeletal hyperphosphorylated protein tau) in AD brains are associated with reactive astrocytes and activated microglial cells, which overexpress cytokines and acute-phase proteins. |
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Formal Description Interaction-ID: 154871 |
gene/protein increases_quantity of phenotype |