General Information:

Id: 2,278
Diseases: Alzheimer disease - [OMIM]
Mammalia
review
Reference: Heneka MT et al.(2011) Molecular mechanisms and therapeutic application of NSAIDs and derived compounds in Alzheimers disease. Curr Alzheimer Res 8: 115-131 [PMID: 21345168]

Interaction Information:

Comment The intake of non-steroidal anti-inflammatory drugs (NSAIDs) reduce the risk and delay the onset of AD. But neither the ideal time point for treatment, nor the exact mechanism of interaction has yet been identified. Some therapeutic studies testing NSAID efficacy in AD patients have not yielded positive results.
Formal Description
Interaction-ID: 19437

drug/chemical compound

NSAID

decreases_activity of

Comment The intake of non-steroidal anti-inflammatory drugs (NSAIDs) reduce the risk and delay the onset of AD. But neither the ideal time point for treatment, nor the exact mechanism of interaction has yet been identified. Some therapeutic studies testing NSAID efficacy in AD patients have not yielded positive results.
Formal Description
Interaction-ID: 19438

drug/chemical compound

NSAID

decreases_activity of

Comment Abeta plaques within the brain are populated by abundant, activated microglia and astrocytes.
Formal Description
Interaction-ID: 19442

interacts (colocalizes) with

tissue/cell line

microglia

Comment Abeta plaques within the brain are populated by abundant, activated microglia and astrocytes.
Formal Description
Interaction-ID: 19461

interacts (colocalizes) with

tissue/cell line

astrocyte

Comment Microglial activation is accompanied by the secretion of inflammatory cytokines and chemokines including interleukin (IL)-1beta, IL-6, monocyte chemotactic protein-1 (MCP-1), and tumor necrosis factor (TNF)-alpha.
Formal Description
Interaction-ID: 19462

increases_activity of

Comment Microglial activation is accompanied by the secretion of inflammatory cytokines and chemokines including interleukin (IL)-1beta, IL-6, monocyte chemotactic protein-1 (MCP-1), and tumor necrosis factor (TNF)-alpha.
Formal Description
Interaction-ID: 19463

increases_activity of

Comment Microglial activation is accompanied by the secretion of inflammatory cytokines and chemokines including interleukin (IL)-1beta, IL-6, monocyte chemotactic protein-1 (MCP-1), and tumor necrosis factor (TNF)-alpha.
Formal Description
Interaction-ID: 19464

increases_quantity of

gene/protein

IL1B

Drugbank entries Show/Hide entries for IL1B
Comment Microglial activation is accompanied by the secretion of inflammatory cytokines and chemokines including interleukin (IL)-1beta, IL-6, monocyte chemotactic protein-1 (MCP-1), and tumor necrosis factor (TNF)-alpha.
Formal Description
Interaction-ID: 19465

increases_quantity of

gene/protein

IL6

Drugbank entries Show/Hide entries for IL6
Comment Microglial activation is accompanied by the secretion of inflammatory cytokines and chemokines including interleukin (IL)-1beta, IL-6, monocyte chemotactic protein-1 (MCP-1), and tumor necrosis factor (TNF)-alpha.
Formal Description
Interaction-ID: 19467

increases_quantity of

gene/protein

CCL2

Drugbank entries Show/Hide entries for CCL2
Comment Microglial activation is accompanied by the secretion of inflammatory cytokines and chemokines including interleukin (IL)-1beta, IL-6, monocyte chemotactic protein-1 (MCP-1), and tumor necrosis factor (TNF)-alpha.
Formal Description
Interaction-ID: 19468

increases_quantity of

gene/protein

TNF

Drugbank entries Show/Hide entries for TNF
Comment PPAR-gamma mRNA levels are elevated in AD patients.
Formal Description
Interaction-ID: 19469

increases_expression of

gene/protein

PPARG

Drugbank entries Show/Hide entries for PPARG
Comment NSAID (Non-steroid antiinflammatory drug) is able to activate the receptor PPAR-gamma.
Formal Description
Interaction-ID: 19473

drug/chemical compound

NSAID

increases_activity of

gene/protein

PPARG

Drugbank entries Show/Hide entries for PPARG
Comment PPAR-gamma activation in microglial cells suppressed inflammatory cytokine expression, iNOS expression and NO production as well as inhibited COX2 and therefore the generation of prostanoids.
Formal Description
Interaction-ID: 19474

gene/protein

PPARG

decreases_expression of

gene/protein

Cytokine

Drugbank entries Show/Hide entries for PPARG
Comment PPAR-gamma activation in microglial cells suppressed inflammatory cytokine expression, iNOS expression and NO production as well as inhibited COX2 and therefore the generation of prostanoids.
Formal Description
Interaction-ID: 19475

gene/protein

PPARG

decreases_expression of

gene/protein

NOS2

Drugbank entries Show/Hide entries for PPARG or NOS2
Comment PPAR-gamma activation in microglial cells suppressed inflammatory cytokine expression, iNOS expression and NO production as well as inhibited COX2 and therefore the generation of prostanoids.
Formal Description
Interaction-ID: 19481

gene/protein

PPARG

is localized in

tissue/cell line

microglia

Drugbank entries Show/Hide entries for PPARG
Comment PPAR-gamma activation in microglial cells suppressed inflammatory cytokine expression, iNOS expression and NO production as well as inhibited COX2 and therefore the generation of prostanoids.
Formal Description
Interaction-ID: 19482

gene/protein

PPARG

decreases_quantity of

drug/chemical compound

NO

Drugbank entries Show/Hide entries for PPARG
Comment PPAR-gamma activation in microglial cells suppressed inflammatory cytokine expression, iNOS expression and NO production as well as inhibited COX2 and therefore the generation of prostanoids.
Formal Description
Interaction-ID: 19485

gene/protein

PPARG

decreases_activity of

gene/protein

PTGS2

Drugbank entries Show/Hide entries for PPARG or PTGS2
Comment PPAR-gamma activation in microglial cells suppressed inflammatory cytokine expression, iNOS expression and NO production as well as inhibited COX2 and therefore the generation of prostanoids.
Formal Description
Interaction-ID: 19487

gene/protein

PPARG

affects_quantity of

drug/chemical compound

Prostanoid

Drugbank entries Show/Hide entries for PPARG
Comment Abeta42 levels were only significantly lowered for ibuprofen treated animals, but a trend was observed for pioglitazone.
Formal Description
Interaction-ID: 19533

drug/chemical compound

Ibuprofen

decreases_quantity of

Drugbank entries Show/Hide entries for Ibuprofen
Comment Abeta42 levels were only significantly lowered for ibuprofen treated animals, but only a trend was observed for pioglitazone due to poor drug penetration into the brain.
Formal Description
Interaction-ID: 19534

drug/chemical compound

Pioglitazone

affects_quantity of

Drugbank entries Show/Hide entries for Pioglitazone
Comment Treatment with larger doses of pioglitazone in aged APPV717I transgenic mice significantly decreased microglial and astroglial activation as well as Abeta plaque burden.
Formal Description
Interaction-ID: 19535

drug/chemical compound

Pioglitazone

decreases_activity of

in aged APPV717I transgenic mice
Drugbank entries Show/Hide entries for Pioglitazone
Comment Treatment with larger doses of pioglitazone in aged APPV717I transgenic mice significantly decreased microglial and astroglial activation as well as Abeta plaque burden.
Formal Description
Interaction-ID: 19536

drug/chemical compound

Pioglitazone

decreases_activity of

in aged APPV717I transgenic mice
Drugbank entries Show/Hide entries for Pioglitazone
Comment Treatment with larger doses of pioglitazone in aged APPV717I transgenic mice significantly decreased microglial and astroglial activation as well as Abeta plaque burden.
Formal Description
Interaction-ID: 19537

drug/chemical compound

Pioglitazone

decreases_quantity of

in aged APPV717I transgenic mice
Drugbank entries Show/Hide entries for Pioglitazone
Comment In mouse models, overexpressing the Swedish and Indiana mutations of human APP, pioglitazone rescued cerebral dysfunction and ameliorated glial activation, oxidative stress and finally cholinergic innervation.
Formal Description
Interaction-ID: 19538

drug/chemical compound

Pioglitazone

decreases_activity of

phenotype

cerebral dysfunction

in mouse models overexpressing the Swedish and Indiana mutations of human APP
Drugbank entries Show/Hide entries for Pioglitazone
Comment In mouse models, overexpressing the Swedish and Indiana mutations of human APP, pioglitazone rescued cerebral dysfunction and ameliorated glial activation, oxidative stress and finally cholinergic innervation.
Formal Description
Interaction-ID: 19539

drug/chemical compound

Pioglitazone

affects_activity of

in mouse models overexpressing the Swedish and Indiana mutations of human APP
Drugbank entries Show/Hide entries for Pioglitazone
Comment In mouse models, overexpressing the Swedish and Indiana mutations of human APP, pioglitazone rescued cerebral dysfunction and ameliorated glial activation, oxidative stress and finally cholinergic innervation.
Formal Description
Interaction-ID: 19540

drug/chemical compound

Pioglitazone

affects_activity of

in mouse models overexpressing the Swedish and Indiana mutations of human APP
Drugbank entries Show/Hide entries for Pioglitazone
Comment In mouse models, overexpressing the Swedish and Indiana mutations of human APP, pioglitazone rescued cerebral dysfunction and ameliorated glial activation, oxidative stress and finally cholinergic innervation.
Formal Description
Interaction-ID: 19541

drug/chemical compound

Pioglitazone

affects_activity of

process

innervation

overexpressing the Swedish and Indiana mutations of human APP
Drugbank entries Show/Hide entries for Pioglitazone
Comment Oral pioglitazone treatment of APP transgenic mice reduced BACE1 transcription and expression.
Formal Description
Interaction-ID: 19542

drug/chemical compound

Pioglitazone

decreases_expression of

gene/protein

BACE1

in APP transgenic mice
Drugbank entries Show/Hide entries for Pioglitazone or BACE1
Comment PPAR-gamma is associated with enhanced Abeta clearance.
Formal Description
Interaction-ID: 19543

gene/protein

PPARG

increases_activity of

Drugbank entries Show/Hide entries for PPARG
Comment Rosiglitazone treatment of Tg2576 mice resulted in behavioural improvement in these animals as well as in reduction of Abeta (1-42) in the brain.
Formal Description
Interaction-ID: 19546

drug/chemical compound

Rosiglitazone

decreases_activity of

in Tg2576 mice
Drugbank entries Show/Hide entries for Rosiglitazone
Comment Rosiglitazone treatment of Tg2576 mice resulted in behavioural improvement in these animals as well as in reduction of Abeta (1-42) in the brain.
Formal Description
Interaction-ID: 19547

drug/chemical compound

Rosiglitazone

affects_activity of

process

behavior

in Tg2576 mice
Drugbank entries Show/Hide entries for Rosiglitazone
Comment Rosiglitazone treatment of Tg2576 mice resulted in behavioural improvement in these animals as well as in reduction of Abeta (1-42) in the brain.
Formal Description
Interaction-ID: 19548

drug/chemical compound

Rosiglitazone

decreases_quantity of

in brain; of Tg2576 mice
Drugbank entries Show/Hide entries for Rosiglitazone
Comment Treatment with rosiglitazone for 34 months enhanced spatial working and reference memory.
Formal Description
Interaction-ID: 19549

drug/chemical compound

Rosiglitazone

increases_activity of

process

memory

(spatial working and reference memory)
Drugbank entries Show/Hide entries for Rosiglitazone
Comment Rosiglitazone drug treatment was associated with a 25 % reduction in Abeta (1-42) levels, however Abeta (1-40) levels remained unchanged.
Formal Description
Interaction-ID: 19550

drug/chemical compound

Rosiglitazone

decreases_quantity of

Drugbank entries Show/Hide entries for Rosiglitazone
Comment Rosiglitazone drug treatment was associated with a 25 % reduction in Abeta (1-42) levels, however Abeta (1-40) levels remained unchanged.
Formal Description
Interaction-ID: 19551

drug/chemical compound

Rosiglitazone

NOT affects_quantity of

Drugbank entries Show/Hide entries for Rosiglitazone
Comment IDE is a Abeta degrading metalloprotease, that has been genetically linked to AD.
Formal Description
Interaction-ID: 19552

gene/protein

IDE

decreases_quantity of

gene/protein

Amyloid beta peptide

Drugbank entries Show/Hide entries for IDE
Comment IDE is a Abeta degrading metalloprotease, that has been genetically linked to AD.
Formal Description
Interaction-ID: 19553

gene/protein

IDE

affects_activity of

Drugbank entries Show/Hide entries for IDE
Comment Rosiglitazone therapy improves cognition in a subset of AD patients.
Formal Description
Interaction-ID: 19593

drug/chemical compound

Rosiglitazone

decreases_activity of

phenotype

cognitive impairment

in a subset of AD patients
Drugbank entries Show/Hide entries for Rosiglitazone
Comment AD risk and memory impairment is associated with hyperinsulinemia, and insulin resistance, features which characterize type II diabetes.
Formal Description
Interaction-ID: 19594

cooccurs with

Comment AD risk and memory impairment is associated with hyperinsulinemia, and insulin resistance, features which characterize type II diabetes.
Formal Description
Interaction-ID: 19595
Comment The canonical targets of all NSAIDs (Non-steroid antiinflammatory drugs) are both isoforms of cyclooxygenase, COX-1 and COX-2.
Formal Description
Interaction-ID: 19598

drug/chemical compound

NSAID

affects_activity of

gene/protein

PTGS1

Drugbank entries Show/Hide entries for PTGS1
Comment The canonical targets of all NSAIDs (Non-steroid antiinflammatory drugs) are both isoforms of cyclooxygenase, COX-1 and COX-2.
Formal Description
Interaction-ID: 19617

drug/chemical compound

NSAID

affects_activity of

gene/protein

PTGS2

Drugbank entries Show/Hide entries for PTGS2
Comment COX-2 is mainly expressed in neurons in the human brain and decreases in later stages of AD.
Formal Description
Interaction-ID: 27776

gene/protein

PTGS2

is localized in

tissue/cell line

neuron

in human brain
Drugbank entries Show/Hide entries for PTGS2
Comment COX-2 is mainly expressed in neurons in the human brain and decreases in later stages of AD.
Formal Description
Interaction-ID: 27779

decreases_expression of

gene/protein

PTGS2

in human brain
Drugbank entries Show/Hide entries for PTGS2
Comment COX-1 is prominently expressed by microglia in the human brain and is modestly elevated in AD.
Formal Description
Interaction-ID: 27782

tissue/cell line

microglia

increases_expression of

gene/protein

PTGS1

in human brain
Drugbank entries Show/Hide entries for PTGS1
Comment COX-1 is prominently expressed by microglia in the human brain and is modestly elevated in AD.
Formal Description
Interaction-ID: 27789

increases_expression of

gene/protein

PTGS1

in human brain
Drugbank entries Show/Hide entries for PTGS1
Comment Triflusal, the COX-1 selective inhibitor in AD animal models, showed a slight reduction of amyloid pathology but a marked effect on inflammatory marker, axonal pathology and cognition.
Formal Description
Interaction-ID: 27790

drug/chemical compound

Triflusal

decreases_activity of

gene/protein

PTGS1

in AD
Drugbank entries Show/Hide entries for Triflusal or PTGS1