General 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 in AD brains are associated with reactive astrocytes and activated microglial cells, which overexpress cytokines and acute-phase proteins.
Formal Description
Interaction-ID: 7074

affects_activity of

in AD brain
Comment Senile plaques in AD brains are associated with reactive astrocytes and activated microglial cells, which overexpress cytokines and acute-phase proteins.
Formal Description
Interaction-ID: 7079

affects_activity of

in AD brain
Comment Senile plaques in AD brains are associated with reactive astrocytes and activated microglial cells, which overexpress cytokines and acute-phase proteins.
Formal Description
Interaction-ID: 7080

affects_activity of

in AD brain
Comment Microglial activation can be due to local or systemic inflammation.
Formal Description
Interaction-ID: 7094

affects_activity of

Comment Cytokines are critical in the pathophysiology of AD.
Formal Description
Interaction-ID: 7122

gene/protein

Cytokine

affects_activity of

Comment In transgenic AD-prone mice, overexpression of TGF-beta reduced plaque burden.
Formal Description
Interaction-ID: 7123

gene/protein

TGFB1

decreases_quantity of

in transgenic AD-prone mice; if TGFBR1 is overexpressed
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.
Formal Description
Interaction-ID: 7243

gene/protein mutant

APOE (isoform E4)

increases_activity of

Comment The APO-epsilon4 allele accelerates amyloid deposition and promotes Abeta aggregation in cholesterol-rich lipid rafts, enhancing aggregation into senile plaques.
Formal Description
Interaction-ID: 7344

gene/protein mutant

APOE (isoform E4)

increases_quantity of

Comment The APO-epsilon4 allele accelerates amyloid deposition and promotes Abeta aggregation in cholesterol-rich lipid rafts, enhancing aggregation into senile plaques.
Formal Description
Interaction-ID: 7345

gene/protein mutant

APOE (isoform E4)

increases_activity of

Comment High cholesterol levels at midlife are a considerable risk factor for dementia/AD in most of longterm follow-up studies.
Formal Description
Interaction-ID: 7346

increases_activity of

High cholesterol levels at midlife are a considerable risk factor for dementia/AD.
Comment High cholesterol levels at midlife are a considerable risk factor for dementia/AD in most of longterm follow-up studies.
Formal Description
Interaction-ID: 7348

increases_activity of

disease

Dementia

High cholesterol levels at midlife are a considerable risk factor for dementia/AD.
Comment Increased cholesterol leads to increased cleavage of APP and increased Abeta production.
Formal Description
Interaction-ID: 7349

increases_processing of

gene/protein

APP

Drugbank entries Show/Hide entries for APP
Comment Increased cholesterol leads to increased cleavage of APP and increased Abeta production.
Formal Description
Interaction-ID: 7350

increases_quantity of

gene/protein

Amyloid beta peptide

Comment Reduction of cellular cholesterol decreases the gamma-secretase activity, which is responsible for Abeta generation.
Formal Description
Interaction-ID: 7351

phenotype

decreased cholesterol homeostasis

decreases_activity of

Comment Reduction of cellular cholesterol decreases the gamma-secretase activity, which is responsible for Abeta generation.
Formal Description
Interaction-ID: 7355

increases_quantity of

gene/protein

Amyloid beta peptide

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.
Formal Description
Interaction-ID: 7514

affects_activity of

in hippocampus (BTO:0000601)
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.
Formal Description
Interaction-ID: 7525

gene/protein

HMOX1

affects_activity of

HO-1 expression in AD patients brain is significantly increased
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.
Formal Description
Interaction-ID: 7533

gene/protein

HMOX1

affects_quantity of

in AD brain
Drugbank entries Show/Hide entries for HMOX1
Comment Activation of HO-1 in neurons is strongly protective against oxidative damage and cell death.
Formal Description
Interaction-ID: 7535

gene/protein

HMOX1

decreases_activity of

process

cell death

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).
Formal Description
Interaction-ID: 7571

drug/chemical compound

Curcumin

decreases_activity of

process

lipid peroxidation

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).
Formal Description
Interaction-ID: 7574

drug/chemical compound

Curcumin

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.
Formal Description
Interaction-ID: 7577

drug/chemical compound

Curcumin

decreases_activity of

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: 7579

drug/chemical compound

Curcumin

decreases_activity of

complex/PPI

NF-kappaB complex

Curcumin inhibits cyclooxygenase enzymes and reduces the activation of nuclear transcription factor NF-kappaB.
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.
Formal Description
Interaction-ID: 7580

drug/chemical compound

Carnosol

increases_expression of

gene/protein

HMOX1

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.
Formal Description
Interaction-ID: 7581

drug/chemical compound

Carnosol

affects_activity of

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.
Formal Description
Interaction-ID: 7582

drug/chemical compound

Zerumbone

increases_expression of

gene/protein

HMOX1

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.
Formal Description
Interaction-ID: 7583

drug/chemical compound

Zerumbone

affects_activity of

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.
Formal Description
Interaction-ID: 7584

drug/chemical compound

Resveratrol

increases_expression of

gene/protein

HMOX1

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.
Formal Description
Interaction-ID: 7585

drug/chemical compound

Resveratrol

affects_activity of

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.
Formal Description
Interaction-ID: 7586

drug/chemical compound

Rosolic acid

increases_expression of

gene/protein

HMOX1

Rosolic acid (Pubchem: 10375289)
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.
Formal Description
Interaction-ID: 7587

drug/chemical compound

Rosolic acid

affects_activity of

Rosolic acid (Pubchem: 10375289)
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.
Formal Description
Interaction-ID: 7588

drug/chemical compound

Sulforaphane

increases_expression of

gene/protein

HMOX1

1-Isothiocyanato-4-methylsulfinylbutane
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.
Formal Description
Interaction-ID: 7589

drug/chemical compound

Sulforaphane

affects_activity of

1-Isothiocyanato-4-methylsulfinylbutane
Comment Activation of HO-1 in neurons is strongly protective against oxidative damage and cell death.
Formal Description
Interaction-ID: 20816

gene/protein

HMOX1

decreases_activity of

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.
Formal Description
Interaction-ID: 20818

drug/chemical compound

Rosolic acid

decreases_activity of

Rosolic acid (Pubchem: 10375289)
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.
Formal Description
Interaction-ID: 20819

drug/chemical compound

Resveratrol

decreases_activity of

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.
Formal Description
Interaction-ID: 20820

drug/chemical compound

Zerumbone

decreases_activity of

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.
Formal Description
Interaction-ID: 20821

drug/chemical compound

Sulforaphane

decreases_activity of

1-Isothiocyanato-4-methylsulfinylbutane
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.
Formal Description
Interaction-ID: 20822

drug/chemical compound

Carnosol

decreases_activity of

Comment In transgenic AD-prone mice, overexpression of TGF-beta reduced plaque burden.
Formal Description
Interaction-ID: 79061

gene/protein

TGFB1

increases_activity of

in transgenic AD-prone mice; if TGFBR1 is overexpressed
Drugbank entries Show/Hide entries for TGFB1
Comment Reduction of cellular cholesterol decreases the gamma-secretase activity, which is responsible for Abeta generation.
Formal Description
Interaction-ID: 80460

drug/chemical compound

Cholesterol

increases_activity of

Drugbank entries Show/Hide entries for Cholesterol
Comment Increased cholesterol leads to increased cleavage of APP and increased Abeta production.
Formal Description
Interaction-ID: 82834

decreases_quantity of

gene/protein

APP

via increased APP cleavage
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

Curcumin

decreases_activity of

Curcumin reduces the activation of nuclear transcription factor NF-kappaB.