General Information:

Id: 3,792 (click here to show other Interactions for entry)
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 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 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 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 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 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 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 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 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 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