General Information:

Id: 3,792
Diseases: Alzheimer disease - [OMIM]
Mammalia
review
Reference: Srikanth V et al.(2011) Advanced glycation endproducts and their receptor RAGE in Alzheimers disease Neurobiol. Aging 32: 763-777 [PMID: 19464758]

Interaction Information:

Comment Accumulation of AGEs in cells and tissues is a normal feature of aging, but is accelerated in AD.
Formal Description
Interaction-ID: 37438

increases_quantity of

drug/chemical compound

Advanced glycation end-product

in cells and tissues
Comment In AD, AGEs can be detected in pathological deposits such as amyloid plaques and neurofibrillary tangles.
Formal Description
Interaction-ID: 37454

drug/chemical compound

Advanced glycation end-product

is localized in

in AD patients
Comment In AD, AGEs can be detected in pathological deposits such as amyloid plaques and neurofibrillary tangles.
Formal Description
Interaction-ID: 37455

drug/chemical compound

Advanced glycation end-product

is localized in

in AD patients
Comment Oxidative stress and AGEs initiate a positive feedback loop.
Formal Description
Interaction-ID: 37456

increases_activity of

drug/chemical compound

Advanced glycation end-product

Comment Oxidative stress and AGEs initiate a positive feedback loop.
Formal Description
Interaction-ID: 37457

drug/chemical compound

Advanced glycation end-product

increases_activity of

Comment The formation of AGEs is accelerated by transition metals, such as copper and iron, which oxidize the protein-bound Amadori products or the monosaccharides directly in solution.
Formal Description
Interaction-ID: 37471

drug/chemical compound

Iron

increases_quantity of

drug/chemical compound

Advanced glycation end-product

Comment AGE formation is irreversible and causes protease-resistant crosslinking of peptides and proteins, leading to protein deposition and amyloidosis.
Formal Description
Interaction-ID: 37472

drug/chemical compound

Advanced glycation end-product

increases_activity of

phenotype

amyloidosis

Comment The formation of AGEs is accelerated by transition metals, such as copper and iron, which oxidize the protein-bound Amadori products or the monosaccharides directly in solution.
Formal Description
Interaction-ID: 37473

drug/chemical compound

Copper

increases_quantity of

drug/chemical compound

Advanced glycation end-product

Comment AGEs have been detected in vascular walls, lipoproteins and lipid constituents, where they lead to macroangiopathy, microangiopathy and amyloidosis.
Formal Description
Interaction-ID: 37474

drug/chemical compound

Advanced glycation end-product

increases_activity of

Comment AGEs are localized in pyramidal neurons.
Formal Description
Interaction-ID: 37475

drug/chemical compound

Advanced glycation end-product

is localized in

tissue/cell line

pyramidal neuron

Comment In the AD brain, extra neuroperikaryal AGE (carboxymethyllysine (CML) and pentosidine) deposits are co-localized with glial fibrillary acidic protein-positive astrocytes.
Formal Description
Interaction-ID: 37476

drug/chemical compound

Advanced glycation end-product

interacts (colocalizes) with

tissue/cell line

astrocyte

in AD brain; with glial fibrillary acidic protein-positive astrocytes
Comment Nearly all of those neurons which show diffuse cytosolic AGE immunoreactivity also contain hyperphosphorylated Tau, suggesting a link between AGE accumulation and the formation of early neurofibrillary tangles.
Formal Description
Interaction-ID: 37482

drug/chemical compound

Advanced glycation end-product

cooccurs with

protein modification

MAPT-hyperphos

suggesting a link between AGE accumulation and the formation of early neurofibrillary tangles
Comment AGEs were colocalized in NFTs (neurofibrillary tangles).
Formal Description
Interaction-ID: 37484

drug/chemical compound

Advanced glycation end-product

interacts (colocalizes) with

Comment The major component of NFT, which consist of paired helical filaments (PHFs), is the microtubule associated protein (MAP)-Tau.
Formal Description
Interaction-ID: 37485

gene/protein

MAPT

affects_quantity of

Microtubule associated protein (MAP)-Tau is the major component of neurofibrillary tangles NFT
Comment In most senile plaques (including diffuse plaques) and cerebral amyloid angiopathy (CAA) from Alzheimer brains, AGEs were observed.
Formal Description
Interaction-ID: 37505

increases_quantity of

drug/chemical compound

Advanced glycation end-product

in AD brain
Comment In AD, CML (carboxymethyllysine) was found to be coexpressed with Tau protein, showing the similar neurofibrillary tangle shape as in neuritic plaques, but not in the core of amyloid plaques. The findings suggest that AGE formation may occur in the early stages of plaque formation in AD, but that AGE-epitopes disappear when the plaque ages or undergoes processing by microglia in the amyloid core.
Formal Description
Interaction-ID: 37506

phenotype

increased carboxymethyllysine level

cooccurs with

phenotype

increased MAPT level

showing the similar neurofibrillary tangle shape as in neuritic plaques, but not in the core of amyloid plaques
Comment AGE formation actively accelerates the conversion of Abeta from monomeric to oligomeric or high molecular weight forms.
Formal Description
Interaction-ID: 37510

drug/chemical compound

Advanced glycation end-product

increases_quantity of

complex/PPI

Amyloid beta peptide (oligomer)

or high molecular weight forms by decreasing Abeta monomeric
Comment AGE formation actively accelerates the conversion of Abeta from monomeric to oligomeric or high molecular weight forms.
Formal Description
Interaction-ID: 37512

drug/chemical compound

Advanced glycation end-product

decreases_quantity of

by conversion of Abeta from monomeric to oligomeric or high molecular weight forms
Comment Formation of covalently crosslinked high molecular weight Abeta oligomers is accelerated by micromolar amounts of copper (Cu+, Cu2+) and iron (Fe2+, Fe3+) ions.
Formal Description
Interaction-ID: 37642

drug/chemical compound

Fe2+

increases_quantity of

complex/PPI

Amyloid beta peptide (oligomer)

The formation of covalently crosslinked high molecular weight Abeta oligomers is accelerated
Comment Formation of covalently crosslinked high molecular weight Abeta oligomers is accelerated by micromolar amounts of copper (Cu+, Cu2+) and iron (Fe2+, Fe3+) ions.
Formal Description
Interaction-ID: 37643

drug/chemical compound

Fe3+

increases_quantity of

complex/PPI

Amyloid beta peptide (oligomer)

The formation of covalently crosslinked high molecular weight Abeta oligomers is accelerated
Comment Formation of covalently crosslinked high molecular weight Abeta oligomers is accelerated by micromolar amounts of copper (Cu+, Cu2+) and iron (Fe2+, Fe3+) ions.
Formal Description
Interaction-ID: 37644

drug/chemical compound

Cu+

increases_quantity of

complex/PPI

Amyloid beta peptide (oligomer)

The formation of covalently crosslinked high molecular weight Abeta oligomers is accelerated
Comment Formation of covalently crosslinked high molecular weight Abeta oligomers is accelerated by micromolar amounts of copper (Cu+, Cu2+) and iron (Fe2+, Fe3+) ions.
Formal Description
Interaction-ID: 37645

drug/chemical compound

Cu2+

increases_quantity of

complex/PPI

Amyloid beta peptide (oligomer)

The formation of covalently crosslinked high molecular weight Abeta oligomers is accelerated
Comment All AGEs tested, regardless of their degree of modification, were found to induce ROS formation in both microglial (CHME-5) and astroglial cells (U373MG), while only highly modified AGEs were able to decrease the cell viability and induce apoptosis.
Formal Description
Interaction-ID: 37646

drug/chemical compound

Advanced glycation end-product

increases_quantity of

drug/chemical compound

Reactive oxygen species

in both microglial (CHME-5) and astroglial cells (U373MG)
Comment All AGEs tested, regardless of their degree of modification, were found to induce ROS formation in both microglial (CHME-5) and astroglial cells (U373MG), while only highly modified AGEs were able to decrease the cell viability and induce apoptosis.
Formal Description
Interaction-ID: 37647

drug/chemical compound

Advanced glycation end-product

increases_activity of

if AGEs are highly modified
Comment Induced by retinoic acid, cells react more susceptible to AGE toxicity through anion superoxide and peroxide generation.
Formal Description
Interaction-ID: 37648

drug/chemical compound

Retinoic acid

increases_activity of

drug/chemical compound

Advanced glycation end-product

through anion superoxide and peroxide generation in cells
Comment The AGE-induced increase in oxidized glutathione could be prevented by the radical scavengers N-acetylcysteine, alpha-lipoic acid and 17beta-estradiol or by application of catalase, indicating that superoxide and hydrogen peroxide production precedes the AGE-mediated depletion of reduced glutathione.
Formal Description
Interaction-ID: 37649

drug/chemical compound

Advanced glycation end-product

increases_quantity of

drug/chemical compound

Glutathione

Drugbank entries Show/Hide entries for
Comment The AGE-induced increase in oxidized glutathione could be prevented by the radical scavengers N-acetylcysteine, alpha-lipoic acid and 17beta-estradiol or by application of catalase, indicating that superoxide and hydrogen peroxide production precedes the AGE-mediated depletion of reduced glutathione.
Formal Description
Interaction-ID: 37650

drug/chemical compound

Acetylcysteine

decreases_quantity of

drug/chemical compound

Glutathione

if increase in oxidized glutathione is AGE-induced
Drugbank entries Show/Hide entries for Acetylcysteine or Glutathione
Comment The AGE-induced increase in oxidized glutathione could be prevented by the radical scavengers N-acetylcysteine, alpha-lipoic acid and 17beta-estradiol or by application of catalase, indicating that superoxide and hydrogen peroxide production precedes the AGE-mediated depletion of reduced glutathione.
Formal Description
Interaction-ID: 37651

drug/chemical compound

Lipoate

decreases_quantity of

drug/chemical compound

Glutathione

if increase in oxidized glutathione is AGE-induced
Drugbank entries Show/Hide entries for
Comment The AGE-induced increase in oxidized glutathione could be prevented by the radical scavengers N-acetylcysteine, alpha-lipoic acid and 17beta-estradiol or by application of catalase, indicating that superoxide and hydrogen peroxide production precedes the AGE-mediated depletion of reduced glutathione.
Formal Description
Interaction-ID: 37652

drug/chemical compound

Estradiol

decreases_quantity of

drug/chemical compound

Glutathione

if increase in oxidized glutathione is AGE-induced
Drugbank entries Show/Hide entries for Estradiol or Glutathione
Comment AGEs decreased the number of cells and increased lactate production.
Formal Description
Interaction-ID: 37653

drug/chemical compound

Advanced glycation end-product

increases_quantity of

drug/chemical compound

Lactate

Comment AGEs can induce the expression of proinflammatory cytokines through nuclear factor KB (NF-KB) dependent pathways via its receptor RAGE.
Formal Description
Interaction-ID: 37671

complex/PPI

NF-kappaB complex

affects_activity of

drug/chemical compound

Advanced glycation end-product

AGEs can induce the expression of proinflammatory cytokines through nuclear factor KB (NF-KB) dependent pathways
Comment AGEs can induce the expression of proinflammatory cytokines through nuclear factor KB (NF-KB) dependent pathways via its receptor RAGE.
Formal Description
Interaction-ID: 37672

drug/chemical compound

Advanced glycation end-product

increases_expression of

gene/protein

Proinflammatory cytokine

through nuclear factor KB (NF-KB) dependent pathways
Comment AGEs can induce the expression of proinflammatory cytokines through nuclear factor KB (NF-KB) dependent pathways via its receptor RAGE. There is evidence that RAGE is up-regulated by its own ligands.
Formal Description
Interaction-ID: 37673

gene/protein

AGER

affects_expression of

gene/protein

Proinflammatory cytokine

Comment Monocyte chemo-attractant protein-1 (MCP-1) and TNF-alpha were both released in a time-dependent manner from both RAW 264.7 macrophages and N-11 microglia upon stimulation with BSA-AGE or lipopolysaccharide (LPS), which was used as a positive control. MCP-1 was also constitutively expressed by unstimulated cells, although at a lower levels.
Formal Description
Interaction-ID: 37674

tissue/cell line

macrophage

affects_quantity of

gene/protein

CCL2

in RAW 264.7 macrophages; upon stimulation with BSA-AGE or lipopolysaccharide (LPS); MCP-1 was also constitutively expressed by unstimulated cells;
Drugbank entries Show/Hide entries for CCL2
Comment Monocyte chemo-attractant protein-1 (MCP-1) and TNF-alpha were both released in a time-dependent manner from both RAW 264.7 macrophages and N-11 microglia upon stimulation with BSA-AGE or lipopolysaccharide (LPS), which was used as a positive control. MCP-1 was also constitutively expressed by unstimulated cells, although at a lower levels.
Formal Description
Interaction-ID: 37675

tissue/cell line

microglia

affects_quantity of

gene/protein

CCL2

in N-11 microglia; upon stimulation with BSA-AGE or lipopolysaccharide (LPS); MCP-1 was also constitutively expressed by unstimulated cells;
Drugbank entries Show/Hide entries for CCL2
Comment Monocyte chemo-attractant protein-1 (MCP-1) and TNF-alpha were both released in a time-dependent manner from both RAW 264.7 macrophages and N-11 microglia upon stimulation with BSA-AGE or lipopolysaccharide (LPS), which was used as a positive control.
Formal Description
Interaction-ID: 37676

tissue/cell line

macrophage

affects_quantity of

gene/protein

TNF

in RAW 264.7 macrophages; upon stimulation with BSA-AGE or lipopolysaccharide (LPS)
Drugbank entries Show/Hide entries for TNF
Comment Monocyte chemo-attractant protein-1 (MCP-1) and TNF-alpha were both released in a time-dependent manner from both RAW 264.7 macrophages and N-11 microglia upon stimulation with BSA-AGE or lipopolysaccharide (LPS), which was used as a positive control.
Formal Description
Interaction-ID: 37677

tissue/cell line

microglia

affects_quantity of

gene/protein

TNF

in N-11 microglia; upon stimulation with BSA-AGE or lipopolysaccharide (LPS)
Drugbank entries Show/Hide entries for TNF
Comment IL-12p70, IFN-gamma and the anti-inflammatory cytokine IL-10 were not induced by either LPS nor BSA (bovine serum albumin) -AGE.
Formal Description
Interaction-ID: 37678

drug/chemical compound

Lipopolysaccharide

NOT affects_quantity of

complex/PPI

IL12A-IL12B complex

Comment IL-12p70, IFN-gamma and the anti-inflammatory cytokine IL-10 were not induced by either LPS nor BSA (bovine serum albumin) -AGE.
Formal Description
Interaction-ID: 37679

drug/chemical compound

Lipopolysaccharide

NOT affects_expression of

gene/protein

IFNG

Drugbank entries Show/Hide entries for IFNG
Comment IL-12p70, IFN-gamma and the anti-inflammatory cytokine IL-10 were not induced by either LPS nor BSA (bovine serum albumin) -AGE.
Formal Description
Interaction-ID: 37680

drug/chemical compound

Lipopolysaccharide

NOT affects_expression of

gene/protein

IL10

Comment IL-12p70, IFN-gamma and the anti-inflammatory cytokine IL-10 were not induced by either LPS nor BSA (bovine serum albumin) -AGE.
Formal Description
Interaction-ID: 37681

drug/chemical compound

Advanced glycation end-product

NOT affects_quantity of

complex/PPI

IL12A-IL12B complex

BSA (bovine serum albumin) -AGE was used
Comment IL-12p70, IFN-gamma and the anti-inflammatory cytokine IL-10 were not induced by either LPS nor BSA (bovine serum albumin) -AGE.
Formal Description
Interaction-ID: 37682

drug/chemical compound

Advanced glycation end-product

NOT affects_expression of

gene/protein

IFNG

BSA (bovine serum albumin) -AGE was used
Drugbank entries Show/Hide entries for IFNG
Comment IL-12p70, IFN-gamma and the anti-inflammatory cytokine IL-10 were not induced by either LPS nor BSA (bovine serum albumin) -AGE.
Formal Description
Interaction-ID: 37683

drug/chemical compound

Advanced glycation end-product

NOT affects_expression of

gene/protein

IL10

BSA (bovine serum albumin) -AGE was used
Comment Isolated microglia and astrocyte cultures from rapid (4h) brain autopsies of AD patients showed increases in the production of pro-IL-1b, IL-6, TNF-alpha, MCP-1, macrophage inflammatory peptide-1a (MIP-1a), IL-8, and macrophage colony-stimulating factor (M-CSF) after exposure to pre-aggregated Abeta (42).
Formal Description
Interaction-ID: 37720

increases_quantity of

gene/protein

pro-IL1B

in isolated microglia and astrocyte cultures; from rapid (4h) brain autopsies of AD patients
Comment Isolated microglia and astrocyte cultures from rapid (4h) brain autopsies of AD patients showed increases in the production of pro-IL-1b, IL-6, TNF-alpha, MCP-1, macrophage inflammatory peptide-1a (MIP-1a), IL-8, and macrophage colony-stimulating factor (M-CSF) after exposure to pre-aggregated Abeta (42).
Formal Description
Interaction-ID: 37721

increases_quantity of

gene/protein

IL6

in isolated microglia and astrocyte cultures; from rapid (4h) brain autopsies of AD patients
Drugbank entries Show/Hide entries for IL6
Comment Isolated microglia and astrocyte cultures from rapid (4h) brain autopsies of AD patients showed increases in the production of pro-IL-1b, IL-6, TNF-alpha, MCP-1, macrophage inflammatory peptide-1a (MIP-1a), IL-8, and macrophage colony-stimulating factor (M-CSF) after exposure to pre-aggregated Abeta (42).
Formal Description
Interaction-ID: 37722

increases_quantity of

gene/protein

TNF

in isolated microglia and astrocyte cultures; from rapid (4h) brain autopsies of AD patients
Drugbank entries Show/Hide entries for TNF
Comment Isolated microglia and astrocyte cultures from rapid (4h) brain autopsies of AD patients showed increases in the production of pro-IL-1b, IL-6, TNF-alpha, MCP-1, macrophage inflammatory peptide-1a (MIP-1a), IL-8, and macrophage colony-stimulating factor (M-CSF) after exposure to pre-aggregated Abeta (42).
Formal Description
Interaction-ID: 37723

increases_quantity of

gene/protein

CCL2

in isolated microglia and astrocyte cultures; from rapid (4h) brain autopsies of AD patients
Drugbank entries Show/Hide entries for CCL2
Comment Isolated microglia and astrocyte cultures from rapid (4h) brain autopsies of AD patients showed increases in the production of pro-IL-1b, IL-6, TNF-alpha, MCP-1, macrophage inflammatory peptide-1a (MIP-1a), IL-8, and macrophage colony-stimulating factor (M-CSF) after exposure to pre-aggregated Abeta (42).
Formal Description
Interaction-ID: 37724

increases_quantity of

gene/protein

CXCL8

in isolated microglia and astrocyte cultures; from rapid (4h) brain autopsies of AD patients
Comment Isolated microglia and astrocyte cultures from rapid (4h) brain autopsies of AD patients showed increases in the production of pro-IL-1b, IL-6, TNF-alpha, MCP-1, macrophage inflammatory peptide-1a (MIP-1a), IL-8, and macrophage colony-stimulating factor (M-CSF) after exposure to pre-aggregated Abeta (42).
Formal Description
Interaction-ID: 37725

increases_quantity of

gene/protein

CCL3

in isolated microglia and astrocyte cultures; from rapid (4h) brain autopsies of AD patients
Comment Isolated microglia and astrocyte cultures from rapid (4h) brain autopsies of AD patients showed increases in the production of pro-IL-1b, IL-6, TNF-alpha, MCP-1, macrophage inflammatory peptide-1a (MIP-1a), IL-8, and macrophage colony-stimulating factor (M-CSF) after exposure to pre-aggregated Abeta (42).
Formal Description
Interaction-ID: 37726

increases_quantity of

gene/protein

M-CSF

in isolated microglia and astrocyte cultures; from rapid (4h) brain autopsies of AD patients
Comment Abeta (42) activates indoleamine 2,3 dioxygenase and kynureninase, which are involved information of the neurotoxin quinolinic acid, and S100A8, a potential pro-inflammatory chemokine.
Formal Description
Interaction-ID: 37727

increases_activity of

gene/protein

KYNU

Drugbank entries Show/Hide entries for KYNU
Comment Abeta (42) activates indoleamine 2,3 dioxygenase and kynureninase, which are involved information of the neurotoxin quinolinic acid, and S100A8, a potential pro-inflammatory chemokine.
Formal Description
Interaction-ID: 37728

increases_activity of

gene/protein

IDO1

Comment Abeta (42) activates indoleamine 2,3 dioxygenase and kynureninase, which are involved information of the neurotoxin quinolinic acid, and S100A8, a potential pro-inflammatory chemokine.
Formal Description
Interaction-ID: 37729

increases_activity of

gene/protein

S100A8

Comment TNF-alpha directly stimulates beta-secretase (BACE1) expression and therefore enhances beta-processing of the amyloid precursor protein (APP) in astrocytes, leading to increased amyloid deposition.
Formal Description
Interaction-ID: 37730

gene/protein

TNF

increases_expression of

gene/protein

BACE1

in astrocytes
Drugbank entries Show/Hide entries for TNF or BACE1
Comment TNF-alpha directly stimulates beta-secretase (BACE1) expression and therefore enhances beta-processing of the amyloid precursor protein (APP) in astrocytes, leading to increased amyloid deposition.
Formal Description
Interaction-ID: 37732

gene/protein

TNF

increases_processing of

gene/protein

APP

in astrocytes; TNF-alpha enhances beta-processing of APP
Drugbank entries Show/Hide entries for TNF or APP
Comment TNF-alpha directly stimulates beta-secretase (BACE1) expression and therefore enhances beta-processing of the amyloid precursor protein (APP) in astrocytes, leading to increased amyloid deposition.
Formal Description
Interaction-ID: 37733

gene/protein

TNF

increases_quantity of

in astrocytes
Drugbank entries Show/Hide entries for TNF
Comment AGEs and TNF-alpha were shown to activate the RAGE gene through the transcription factors NF-kappaB and Sp-1, causing enhanced AGE-RAGE interactions, which would lead to an exacerbation of AGE-RAGE mediated damage.
Formal Description
Interaction-ID: 37734

drug/chemical compound

Advanced glycation end-product

increases_activity of

gene/protein

AGER

through the transcription factors NF-kappaB and Sp-1, causing enhanced AGE-RAGE interactions
Comment AGEs and TNF-alpha were shown to activate the RAGE gene through the transcription factors NF-kappaB and Sp-1, causing enhanced AGE-RAGE interactions, which would lead to an exacerbation of AGE-RAGE mediated damage.
Formal Description
Interaction-ID: 37749

drug/chemical compound

Advanced glycation end-product

increases_activity of

gene/protein

TNF

through the transcription factors NF-kappaB and Sp-1, causing enhanced AGE-RAGE interactions
Drugbank entries Show/Hide entries for TNF
Comment Incubation of microglia with M-CSF and Abeta increased expression of RAGE mRNA in microglia isolated from AD brains. These microglia also expressed M-CSF receptor mRNA.
Formal Description
Interaction-ID: 37752

gene/protein

M-CSF

increases_expression of

gene/protein

AGER

in AD brain microglia
Comment Incubation of microglia with M-CSF and Abeta increased expression of RAGE mRNA in microglia isolated from AD brains. These microglia also expressed M-CSF receptor mRNA.
Formal Description
Interaction-ID: 37775

gene/protein

TNF

increases_expression of

gene/protein

AGER

in AD brain microglia
Drugbank entries Show/Hide entries for TNF
Comment There exists an increase of methylglyoxal levels in AD patients. This could be a consequence of the inhibition of glucose flux downstream of triose phosphates, e.g.in the lower part of glycolysis, the citric acid cycle and the oxidation of generated reducing equivalents through mitochondrial respiration.
Formal Description
Interaction-ID: 37790

increases_quantity of

drug/chemical compound

Methylglyoxal

perhaps due to the inhibition of glucose flux downstream of triose phosphates downstream of triose phosphates, e.g.in the lower part of glycolysis, the citric acid cycle and the oxidation of generated reducing equivalents through mitochondrial respiration
Comment Unchelated transition metals such as copper and iron have been observed loosely bound to amyloid plaques. They increase oxidation of sugars and Amadori products, but foster the aggregation of Abeta peptides, bringing the monomers in close proximity for AGE-induced crosslinking.
Formal Description
Interaction-ID: 37807

affects_quantity of

Unchelated transition metals such as copper and iron have been observed loosely bound to amyloid plaques.
Comment AGEs could contribute to the inability of microglia to clear plaques by introducing crosslinks to Abeta and other plaque associated proteins which makes it difficult to take up and degrade Abeta by inhibiting lysosomal proteases such as cathepsin D.
Formal Description
Interaction-ID: 37808

drug/chemical compound

Advanced glycation end-product

affects_activity of

tissue/cell line

microglia

Comment Microglia express receptors that promote the clearance and phagocytosis of Abeta, such as class A scavenger receptor (SRA) and CD36.
Formal Description
Interaction-ID: 37818

tissue/cell line

microglia

increases_expression of

complex/PPI

Class A scavenger receptor

SRA promotes the clearance and phagocytosis of Abeta.
Comment Microglia express receptors that promote the clearance and phagocytosis of Abeta, such as class A scavenger receptor (SRA) and CD36.
Formal Description
Interaction-ID: 37820

tissue/cell line

microglia

increases_expression of

gene/protein

CD36

CD36 promotes the clearance and phagocytosis of Abeta.
Comment Microglia express receptors that promote the clearance and phagocytosis of Abeta, such as class A scavenger receptor (SRA) and CD36.
Formal Description
Interaction-ID: 37821

gene/protein

CD36

affects_activity of

process

phagocytosis

CD36 promotes the clearance and phagocytosis of Abeta.
Comment Microglia express receptors that promote the clearance and phagocytosis of Abeta, such as class A scavenger receptor (SRA) and CD36.
Formal Description
Interaction-ID: 37822

complex/PPI

Class A scavenger receptor

affects_activity of

process

phagocytosis

SRA promotes the clearance and phagocytosis of Abeta.
Comment Microglia express receptors that promote the clearance and phagocytosis of Abeta, such as class A scavenger receptor (SRA) and CD36.
Formal Description
Interaction-ID: 37823

gene/protein

CD36

increases_activity of

CD36 promotes the clearance and phagocytosis of Abeta.
Comment Microglia express receptors that promote the clearance and phagocytosis of Abeta, such as class A scavenger receptor (SRA) and CD36.
Formal Description
Interaction-ID: 37824

complex/PPI

Class A scavenger receptor

increases_activity of

SRA promotes the clearance and phagocytosis of Abeta.
Comment Invading macrophages from the periphery can restrict senile plaque formation by phagocytosis of Abeta. The paradox is that microglia (resident macrophages of the brain and spinal cord) may ultimately contribute towards plaque formation due to their failure to clear Abeta efficiently.
Formal Description
Interaction-ID: 37826

tissue/cell line

macrophage

decreases_quantity of

by phagocytosis of Abeta
Comment Microglia from older transgenic presenilin 1 (PS1)-APP mice showed reduced expression of the Abeta-binding scavenger receptors SRA, CD36 as well as RAGE and the Abeta degrading enzymes insulysin, neprilysin, and MMP9, compared with their littermate controls.
Formal Description
Interaction-ID: 37827

process

aging

decreases_activity of

tissue/cell line

microglia

in older transgenic presenilin 1 (PS1)-APP mice
Comment Microglia from older transgenic presenilin 1 (PS1)-APP mice showed reduced expression of the Abeta-binding scavenger receptors SRA, CD36 as well as RAGE and the Abeta degrading enzymes insulysin, neprilysin, and MMP9, compared with their littermate controls.
Formal Description
Interaction-ID: 37829

process

aging

decreases_expression of

complex/PPI

Class A scavenger receptor

in microglia; in older transgenic presenilin 1 (PS1)-APP mice
Comment Microglia from older transgenic presenilin 1 (PS1)-APP mice showed reduced expression of the Abeta-binding scavenger receptors SRA, CD36 as well as RAGE and the Abeta degrading enzymes insulysin, neprilysin, and MMP9, compared with their littermate controls.
Formal Description
Interaction-ID: 37830

process

aging

decreases_expression of

gene/protein

AGER

in microglia; in older transgenic presenilin 1 (PS1)-APP mice
Comment Microglia from older transgenic presenilin 1 (PS1)-APP mice showed reduced expression of the Abeta-binding scavenger receptors SRA, CD36 as well as RAGE and the Abeta degrading enzymes insulysin, neprilysin, and MMP9, compared with their littermate controls.
Formal Description
Interaction-ID: 37831

process

aging

decreases_expression of

gene/protein

CD36

in microglia; in older transgenic presenilin 1 (PS1)-APP mice
Comment Microglia from older transgenic presenilin 1 (PS1)-APP mice showed reduced expression of the Abeta-binding scavenger receptors SRA, CD36 as well as RAGE and the Abeta degrading enzymes insulysin, neprilysin, and MMP9, compared with their littermate controls.
Formal Description
Interaction-ID: 37832

process

aging

decreases_expression of

gene/protein

IDE

in microglia; in older transgenic presenilin 1 (PS1)-APP mice
Drugbank entries Show/Hide entries for IDE
Comment Microglia from older transgenic presenilin 1 (PS1)-APP mice showed reduced expression of the Abeta-binding scavenger receptors SRA, CD36 as well as RAGE and the Abeta degrading enzymes insulysin, neprilysin, and MMP9, compared with their littermate controls.
Formal Description
Interaction-ID: 37833

process

aging

decreases_expression of

gene/protein

MME

in microglia; in older transgenic presenilin 1 (PS1)-APP mice
Drugbank entries Show/Hide entries for MME
Comment Microglia from older transgenic presenilin 1 (PS1)-APP mice showed reduced expression of the Abeta-binding scavenger receptors SRA, CD36 as well as RAGE and the Abeta degrading enzymes insulysin, neprilysin, and MMP9, compared with their littermate controls.
Formal Description
Interaction-ID: 37834

process

aging

decreases_expression of

gene/protein

MMP9

in microglia; in older transgenic presenilin 1 (PS1)-APP mice
Comment Microglia from older transgenic presenilin 1 (PS1)-APP mice showed reduced expression of the Abeta-binding scavenger receptors SRA, CD36 as well as RAGE and the Abeta degrading enzymes insulysin, neprilysin, and MMP9, compared with their littermate controls. These microglia had increased expression levels of IL-1 and TNF-alpha, suggesting an inverse correlation between cytokine production and Abeta clearance.
Formal Description
Interaction-ID: 37835

process

aging

increases_expression of

gene/protein

IL1

in microglia; in older transgenic presenilin 1 (PS1)-APP mice
Comment Microglia from older transgenic presenilin 1 (PS1)-APP mice showed reduced expression of the Abeta-binding scavenger receptors SRA, CD36 as well as RAGE and the Abeta degrading enzymes insulysin, neprilysin, and MMP9, compared with their littermate controls. These microglia had increased expression levels of IL-1 and TNF-alpha, suggesting an inverse correlation between cytokine production and Abeta clearance.
Formal Description
Interaction-ID: 37836

process

aging

increases_expression of

gene/protein

TNF

in microglia; in older transgenic presenilin 1 (PS1)-APP mice
Drugbank entries Show/Hide entries for TNF
Comment Patients with Alzheimer's disease and normal glucose tolerance have been shown to have a stronger insulin secretory response to an oral glucose load than controls, suggesting that they may have increased insulin resistance.
Formal Description
Interaction-ID: 37866

increases_activity of

in AD patients as response to an oral glucose load
Comment The desensitization of neuronal insulin receptors may play a role in AD, as patients with AD have elevated insulin levels in the cerebrospinal fluid under fasting conditions.
Formal Description
Interaction-ID: 37875

increases_activity of

phenotype

increased insulin level

in the cerebrospinal fluid; of AD patients
Comment RAGE expression in capillaries of AD brain is significantly increased compared to control cases.
Formal Description
Interaction-ID: 37879

increases_expression of

gene/protein

AGER

in capillaries of AD brain
Comment There exist significant negative correlations between the Abeta burden of amyloid plaques and RAGE-positive capillaries in AD brains.
Formal Description
Interaction-ID: 37916

gene/protein

AGER

affects_quantity of

in capillaries in AD brain
Comment In AD, most astrocytes contained both AGE- and RAGE-positive granules. In DM patients and control cases, AGE- and RAGE-positive astrocytes were very rare. These findings support the hypothesis that glycated Abeta and RAGE are taken up into astrocytes and degraded through the lysosomal pathway.
Formal Description
Interaction-ID: 37920

gene/protein

AGER

is localized in

tissue/cell line

astrocyte

in Alzheimer disease in form of granules
Comment In AD, most astrocytes contained both AGE- and RAGE-positive granules. In DM patients and control cases, AGE- and RAGE-positive astrocytes were very rare. These findings support the hypothesis that glycated Abeta and RAGE are taken up into astrocytes and degraded through the lysosomal pathway.
Formal Description
Interaction-ID: 37931

drug/chemical compound

Advanced glycation end-product

is localized in

tissue/cell line

astrocyte

in Alzheimer disease in form of granules
Comment RAGE expression was shown to be present on microglia and neurons of the hippocampus, entorhinal cortex, and superior frontal gyrusin AD and nondemented (ND) individuals, with obviously increased numbers of RAGE- immunoreactive microglia in AD.
Formal Description
Interaction-ID: 37983

tissue/cell line

microglia

increases_expression of

gene/protein

AGER

in the hippocampus, entorhinal cortex, and superior frontal gyrusin; of AD patients and nondemented (ND) individuals
Comment RAGE expression was shown to be present on microglia and neurons of the hippocampus, entorhinal cortex, and superior frontal gyrusin AD and nondemented (ND) individuals, with obviously increased numbers of RAGE- immunoreactive microglia in AD.
Formal Description
Interaction-ID: 37985

tissue/cell line

neuron

increases_expression of

gene/protein

AGER

in the hippocampus, entorhinal cortex, and superior frontal gyrusin; of AD patients and nondemented (ND) individuals
Comment Clinical studies have recently shown that higher plasma levels of sRAGE are associated with a reduced risk of diseases related to chronic inflammation and oxidative stress.
Formal Description
Interaction-ID: 37988

mRNA/protein variant

AGER (soluble splice variant)

affects_activity of

Higher plasma levels of sRAGE are associated with a reduced risk of diseases related to chronic inflammation and oxidative stress.
Comment Clinical studies have recently shown that higher plasma levels of sRAGE are associated with a reduced risk of diseases related to chronic inflammation and oxidative stress.
Formal Description
Interaction-ID: 38001

mRNA/protein variant

AGER (soluble splice variant)

affects_activity of

Higher plasma levels of sRAGE are associated with a reduced risk of diseases related to chronic inflammation and oxidative stress.
Comment Some studies showed that sRAGE levels were significantly reduced in the plasma of AD patients compared with either vascular dementia patients or non-demented controls.
Formal Description
Interaction-ID: 38037

decreases_quantity of

in the plasma; of AD patients
Comment A reduced level of circulating sRAGE was measured in patients with mild cognitive impairment.
Formal Description
Interaction-ID: 38040

phenotype

mild cognitive impairment

decreases_quantity of

gene/protein

AGER (soluble splice variant)

Comment Hypothesis: Since nearly all RAGE ligands are mediators of inflammation, sRAGE might be viewed as an endogenous biological anti-inflammatory molecule. Moreover, high sRAGE levels might downregulate excess inflammation as present in many degenerative diseases of the elderly.
Formal Description
Interaction-ID: 38043

none selected

Drugbank entries Show/Hide entries for or
Comment RAGE binds S100 proteins and amphoterin (HMBG-1).
Formal Description
Interaction-ID: 38056

gene/protein

AGER

interacts (colocalizes) with

gene/protein

S100

Comment RAGE binds S100 proteins and amphoterin (HMBG-1).
Formal Description
Interaction-ID: 38059

gene/protein

AGER

interacts (colocalizes) with

gene/protein

HMGB1

Comment Aminoguanidine is an AGE-inhibitor.
Formal Description
Interaction-ID: 38072

drug/chemical compound

Aminoguanidine

decreases_activity of

drug/chemical compound

Advanced glycation end-product

Drugbank entries Show/Hide entries for Aminoguanidine
Comment Tenilsetam (AGE-inhibitor and metal-chelator) reacts with sugars and glycated proteins and acts as an inhibitor of AGE-induced amino acid and protein crosslinking in vitro.
Formal Description
Interaction-ID: 38075

drug/chemical compound

Tenilsetam

decreases_activity of

drug/chemical compound

Advanced glycation end-product

Comment Tenilsetam, aminoguanidine and carnosine significantly inhibit nucleation-dependent polymerization of Abeta peptide with similar efficacy.
Formal Description
Interaction-ID: 38077

drug/chemical compound

Tenilsetam

decreases_activity of

gene/protein

Amyloid beta peptide

Tenilsetam inhibits nucleation-dependent polymerization of Abeta.
Comment Tenilsetam, aminoguanidine and carnosine significantly inhibit nucleation-dependent polymerization of Abeta peptide with similar efficacy.
Formal Description
Interaction-ID: 38083

drug/chemical compound

Aminoguanidine

decreases_activity of

gene/protein

Amyloid beta peptide

Aminoguanidine inhibits nucleation-dependent polymerization of Abeta.
Drugbank entries Show/Hide entries for Aminoguanidine
Comment Tenilsetam, aminoguanidine and carnosine significantly inhibit nucleation-dependent polymerization of Abeta peptide with similar efficacy.
Formal Description
Interaction-ID: 38084

drug/chemical compound

Carnosine

decreases_activity of

gene/protein

Amyloid beta peptide

Carnosine inhibits nucleation-dependent polymerization of Abeta.
Comment RAGE functions as Abeta transporter into the brain and is considered a key target in the inflammatory and neurotoxic cascade which contributes to the progression of AD.
Formal Description
Interaction-ID: 38094

gene/protein

AGER

affects transport of

gene/protein

Amyloid beta peptide

into the brain
Comment Although many epidemiological studies suggest that there is a connection between antioxidants and a reduced risk of AD, only a few trials with single antioxidants including Vitamin E, estrogen, and alpha-lipoic acid have displayed some benefits for AD patients, suggesting that these drugs are only effective in very early stages of the disease.
Formal Description
Interaction-ID: 38230

drug/chemical compound

alpha-Tocopherol

decreases_activity of

Comment Although many epidemiological studies suggest that there is a connection between antioxidants and a reduced risk of AD, only a few trials with single antioxidants including Vitamin E, estrogen, and alpha-lipoic acid have displayed some benefits for AD patients, suggesting that these drugs are only effective in very early stages of the disease.
Formal Description
Interaction-ID: 38231

drug/chemical compound

Estrogen

decreases_activity of

Comment Although many epidemiological studies suggest that there is a connection between antioxidants and a reduced risk of AD, only a few trials with single antioxidants including Vitamin E, estrogen, and alpha-lipoic acid have displayed some benefits for AD patients, suggesting that these drugs are only effective in very early stages of the disease.
Formal Description
Interaction-ID: 38232

drug/chemical compound

Lipoate

decreases_activity of

Comment Accumulation of AGEs in cells and tissues is a normal feature of aging, but is accelerated in AD.
Formal Description
Interaction-ID: 64566

process

aging

increases_activity of

phenotype

increased advanced glycation end-product level