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General Information:

Id:	3,792
Diseases:	Alzheimer disease - [OMIM]
Organism:	Mammalia
Publication type:	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	disease Alzheimer disease 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 phenotype amyloid beta deposits 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 phenotype neurofibrillary tangles in AD patients

Comment	Oxidative stress and AGEs initiate a positive feedback loop.
Formal Description Interaction-ID: 37456	process response to oxidative stress 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 process response to oxidative stress

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 phenotype abnormal blood vessel morphology

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 phenotype neurofibrillary tangles

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 increases_quantity of phenotype neurofibrillary tangles 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	phenotype cerebral amyloid angiopathy 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 gene/protein Amyloid beta peptide (monomer) 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 process apoptotic process 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 disulfide

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 disulfide if increase in oxidized glutathione is AGE-induced
Drugbank entries	Show/Hide entries for Acetylcysteine
Drugbank DB06151	Acetylcysteine reducer

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 disulfide if increase in oxidized glutathione is AGE-induced

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 disulfide if increase in oxidized glutathione is AGE-induced
Drugbank entries	Show/Hide entries for Estradiol
Drugbank DB00783	Estradiol agonist ESR1
Drugbank DB00783	Estradiol not specified NR1I2
Drugbank DB00783	Estradiol agonist ESR2

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
Drugbank DB01055	Mimosine inhibitor CCL2
Drugbank DB01406	Danazol inhibitor CCL2
Drugbank DB01055	Mimosine inhibitor 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
Drugbank DB01055	Mimosine inhibitor CCL2
Drugbank DB01406	Danazol inhibitor CCL2
Drugbank DB01055	Mimosine inhibitor 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
Drugbank DB00005	Etanercept antibody TNF
Drugbank DB00051	Adalimumab antibody TNF
Drugbank DB00065	Infliximab inhibitor TNF
Drugbank DB00608	Chloroquine not specified TNF
Drugbank DB01041	Thalidomide inhibitor TNF
Drugbank DB01296	Glucosamine not specified TNF
Drugbank DB01407	Clenbuterol other/unknown TNF
Drugbank DB01411	Pranlukast other/unknown TNF
Drugbank DB01427	Amrinone inhibitor TNF
Drugbank DB00051	Adalimumab antibody TNF
Drugbank DB00065	Infliximab inhibitor TNF
Drugbank DB01427	Amrinone inhibitor 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
Drugbank DB00005	Etanercept antibody TNF
Drugbank DB00051	Adalimumab antibody TNF
Drugbank DB00065	Infliximab inhibitor TNF
Drugbank DB00608	Chloroquine not specified TNF
Drugbank DB01041	Thalidomide inhibitor TNF
Drugbank DB01296	Glucosamine not specified TNF
Drugbank DB01407	Clenbuterol other/unknown TNF
Drugbank DB01411	Pranlukast other/unknown TNF
Drugbank DB01427	Amrinone inhibitor TNF
Drugbank DB00051	Adalimumab antibody TNF
Drugbank DB00065	Infliximab inhibitor TNF
Drugbank DB01427	Amrinone inhibitor 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
Drugbank DB01250	Olsalazine other IFNG
Drugbank DB01296	Glucosamine not specified 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
Drugbank DB01250	Olsalazine other IFNG
Drugbank DB01296	Glucosamine not specified 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	gene/protein Amyloid beta peptide (42) 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	gene/protein Amyloid beta peptide (42) 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
Drugbank DB01404	Ginseng antagonist IL6
Drugbank DB01404	Ginseng antagonist 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	gene/protein Amyloid beta peptide (42) 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
Drugbank DB00005	Etanercept antibody TNF
Drugbank DB00051	Adalimumab antibody TNF
Drugbank DB00065	Infliximab inhibitor TNF
Drugbank DB00608	Chloroquine not specified TNF
Drugbank DB01041	Thalidomide inhibitor TNF
Drugbank DB01296	Glucosamine not specified TNF
Drugbank DB01407	Clenbuterol other/unknown TNF
Drugbank DB01411	Pranlukast other/unknown TNF
Drugbank DB01427	Amrinone inhibitor TNF
Drugbank DB00051	Adalimumab antibody TNF
Drugbank DB00065	Infliximab inhibitor TNF
Drugbank DB01427	Amrinone inhibitor 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	gene/protein Amyloid beta peptide (42) 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
Drugbank DB01055	Mimosine inhibitor CCL2
Drugbank DB01406	Danazol inhibitor CCL2
Drugbank DB01055	Mimosine inhibitor 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	gene/protein Amyloid beta peptide (42) 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	gene/protein Amyloid beta peptide (42) 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	gene/protein Amyloid beta peptide (42) 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	gene/protein Amyloid beta peptide (42) increases_activity of gene/protein KYNU
Drugbank entries	Show/Hide entries for KYNU
Drugbank DB00114	Pyridoxal Phosphate cofactor KYNU
Drugbank DB00160	L-Alanine not specified KYNU
Drugbank DB02343	3,6,9,12,15-Pentaoxaheptadecane not specified kynU
Drugbank DB07069	3-Hydroxyhippuric acid not specified KYNU
Drugbank DB00160	L-Alanine not specified KYNU
Drugbank DB02343	3,6,9,12,15-Pentaoxaheptadecane not specified 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	gene/protein Amyloid beta peptide (42) 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	gene/protein Amyloid beta peptide (42) 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
Drugbank DB00005	Etanercept antibody TNF
Drugbank DB00051	Adalimumab antibody TNF
Drugbank DB00065	Infliximab inhibitor TNF
Drugbank DB00608	Chloroquine not specified TNF
Drugbank DB01041	Thalidomide inhibitor TNF
Drugbank DB01296	Glucosamine not specified TNF
Drugbank DB01407	Clenbuterol other/unknown TNF
Drugbank DB01411	Pranlukast other/unknown TNF
Drugbank DB01427	Amrinone inhibitor TNF
Drugbank DB00051	Adalimumab antibody TNF
Drugbank DB00065	Infliximab inhibitor TNF
Drugbank DB01427	Amrinone inhibitor TNF
Drugbank DB02378	MMI-175 not specified BACE1
Drugbank DB06930	N-[amino(imino)methyl]-2-(2,5-diphenyl-1 ... not specified BACE1
Drugbank DB07019	N-[(5R,14R)-5-AMINO-5,14-DIMETHYL-4-OXO- ... not specified BACE1
Drugbank DB07089	N-[amino(imino)methyl]-2-[2-(2-chlorophe ... not specified BACE1
Drugbank DB07110	4-(4-FLUOROBENZYL)PIPERIDINE not specified BACE1
Drugbank DB07175	N-{2-methyl-5-[(6-phenylpyrimidin-4-yl)a ... not specified BACE1
Drugbank DB07206	6-[2-(1H-INDOL-6-YL)ETHYL]PYRIDIN-2-AMIN ... not specified BACE1
Drugbank DB07245	6-[2-(3'-METHOXYBIPHENYL-3-YL)ETHYL]PYRI ... not specified BACE1
Drugbank DB07281	N~3~-BENZYLPYRIDINE-2,3-DIAMINE not specified BACE1
Drugbank DB07284	N~3~-(3-PYRIDIN-3-YLBENZYL)PYRIDINE-2,3- ... not specified BACE1
Drugbank DB07303	N~3~-[3-(5-METHOXYPYRIDIN-3-YL)BENZYL]PY ... not specified BACE1
Drugbank DB07345	4-(2-aminoethyl)-2-cyclohexylphenol not specified BACE1
Drugbank DB07346	4-(2-aminoethyl)-2-ethylphenol not specified BACE1
Drugbank DB07415	4-[(1S)-1-(3-fluoro-4-methoxyphenyl)-2-( ... not specified BACE1
Drugbank DB07519	(6R)-2-amino-6-[2-(3'-methoxybiphenyl-3- ... not specified BACE1
Drugbank DB07535	2-amino-6-[2-(1H-indol-6-yl)ethyl]pyrimi ... not specified BACE1
Drugbank DB07573	(2S)-1-(2,5-dimethylphenoxy)-3-morpholin ... not specified BACE1
Drugbank DB07734	N-(1-benzylpiperidin-4-yl)-4-sulfanylbut ... not specified BACE1
Drugbank DB07735	N-[1-(2,6-dimethoxybenzyl)piperidin-4-yl ... not specified BACE1
Drugbank DB07736	(2S)-4-(4-fluorobenzyl)-N-(2-sulfanyleth ... not specified BACE1
Drugbank DB07737	(2S)-4-(4-fluorobenzyl)-N-(3-sulfanylpro ... not specified BACE1
Drugbank DB07738	N-[1-(5-bromo-2,3-dimethoxybenzyl)piperi ... not specified BACE1
Drugbank DB07874	(6S)-2-amino-6-(3'-methoxybiphenyl-3-yl) ... not specified BACE1
Drugbank DB07993	N~3~-[3-(1H-INDOL-6-YL)BENZYL]PYRIDINE-2 ... not specified BACE1
Drugbank DB07994	N~3~-[5-(1H-INDOL-6-YL)-2-(PYRIDIN-2-YLM ... not specified BACE1
Drugbank DB08749	3-(2-AMINO-6-BENZOYLQUINAZOLIN-3(4H)-YL) ... not specified BACE1
Drugbank DB02378	MMI-175 not specified 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
Drugbank DB00005	Etanercept antibody TNF
Drugbank DB00051	Adalimumab antibody TNF
Drugbank DB00065	Infliximab inhibitor TNF
Drugbank DB00608	Chloroquine not specified TNF
Drugbank DB01041	Thalidomide inhibitor TNF
Drugbank DB01296	Glucosamine not specified TNF
Drugbank DB01407	Clenbuterol other/unknown TNF
Drugbank DB01411	Pranlukast other/unknown TNF
Drugbank DB01427	Amrinone inhibitor TNF
Drugbank DB00051	Adalimumab antibody TNF
Drugbank DB00065	Infliximab inhibitor TNF
Drugbank DB01427	Amrinone inhibitor TNF
Drugbank DB02235	Methionine Sulfoxide not specified APP
Drugbank DB02235	Methionine Sulfoxide not specified 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 phenotype amyloid beta deposits in astrocytes
Drugbank entries	Show/Hide entries for TNF
Drugbank DB00005	Etanercept antibody TNF
Drugbank DB00051	Adalimumab antibody TNF
Drugbank DB00065	Infliximab inhibitor TNF
Drugbank DB00608	Chloroquine not specified TNF
Drugbank DB01041	Thalidomide inhibitor TNF
Drugbank DB01296	Glucosamine not specified TNF
Drugbank DB01407	Clenbuterol other/unknown TNF
Drugbank DB01411	Pranlukast other/unknown TNF
Drugbank DB01427	Amrinone inhibitor TNF
Drugbank DB00051	Adalimumab antibody TNF
Drugbank DB00065	Infliximab inhibitor TNF
Drugbank DB01427	Amrinone inhibitor 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
Drugbank DB00005	Etanercept antibody TNF
Drugbank DB00051	Adalimumab antibody TNF
Drugbank DB00065	Infliximab inhibitor TNF
Drugbank DB00608	Chloroquine not specified TNF
Drugbank DB01041	Thalidomide inhibitor TNF
Drugbank DB01296	Glucosamine not specified TNF
Drugbank DB01407	Clenbuterol other/unknown TNF
Drugbank DB01411	Pranlukast other/unknown TNF
Drugbank DB01427	Amrinone inhibitor TNF
Drugbank DB00051	Adalimumab antibody TNF
Drugbank DB00065	Infliximab inhibitor TNF
Drugbank DB01427	Amrinone inhibitor 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
Drugbank DB00005	Etanercept antibody TNF
Drugbank DB00051	Adalimumab antibody TNF
Drugbank DB00065	Infliximab inhibitor TNF
Drugbank DB00608	Chloroquine not specified TNF
Drugbank DB01041	Thalidomide inhibitor TNF
Drugbank DB01296	Glucosamine not specified TNF
Drugbank DB01407	Clenbuterol other/unknown TNF
Drugbank DB01411	Pranlukast other/unknown TNF
Drugbank DB01427	Amrinone inhibitor TNF
Drugbank DB00051	Adalimumab antibody TNF
Drugbank DB00065	Infliximab inhibitor TNF
Drugbank DB01427	Amrinone inhibitor 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	disease Alzheimer disease 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	process transition metal ion binding affects_quantity of phenotype amyloid beta deposits 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	complex/PPI Class A scavenger receptor is_expressed_in tissue/cell line microglia 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	gene/protein CD36 is_expressed_in tissue/cell line microglia 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 process amyloid-beta clearance 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 process amyloid-beta clearance 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 phenotype amyloid beta deposits 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
Drugbank DB00030	Insulin recombinant not specified IDE
Drugbank DB00071	Insulin, porcine not specified IDE
Drugbank DB00626	Bacitracin inhibitor 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
Drugbank DB00616	Candoxatril inhibitor MME
Drugbank DB02062	N-[3-[(1-Aminoethyl)(Hydroxy)Phosphoryl] ... not specified MME
Drugbank DB02557	Phosphoramidon inhibitor MME
Drugbank DB02558	N-(3-Phenyl-2-Sulfanylpropanoyl)Phenylal ... not specified MME
Drugbank DB02597	[2(R,S)-2-Sulfanylheptanoyl]-Phe-Ala not specified MME
Drugbank DB08575	2-[(1S)-1-BENZYL-2-SULFANYLETHYL]-1H-IMI ... not specified MME
Drugbank DB08626	Thiorphan inhibitor MME
Drugbank DB00616	Candoxatril inhibitor MME
Drugbank DB02062	N-[3-[(1-Aminoethyl)(Hydroxy)Phosphoryl] ... not specified MME
Drugbank DB02557	Phosphoramidon inhibitor MME
Drugbank DB02558	N-(3-Phenyl-2-Sulfanylpropanoyl)Phenylal ... not specified MME
Drugbank DB02597	[2(R,S)-2-Sulfanylheptanoyl]-Phe-Ala not specified 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
Drugbank DB00005	Etanercept antibody TNF
Drugbank DB00051	Adalimumab antibody TNF
Drugbank DB00065	Infliximab inhibitor TNF
Drugbank DB00608	Chloroquine not specified TNF
Drugbank DB01041	Thalidomide inhibitor TNF
Drugbank DB01296	Glucosamine not specified TNF
Drugbank DB01407	Clenbuterol other/unknown TNF
Drugbank DB01411	Pranlukast other/unknown TNF
Drugbank DB01427	Amrinone inhibitor TNF
Drugbank DB00051	Adalimumab antibody TNF
Drugbank DB00065	Infliximab inhibitor TNF
Drugbank DB01427	Amrinone inhibitor 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	disease Alzheimer disease increases_activity of process insulin secretion in AD patients; as response to an oral glucose load, suggesting an increased insulin resistance

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	disease Alzheimer disease 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	disease Alzheimer disease 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 phenotype amyloid beta deposits 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	gene/protein AGER is_expressed_in tissue/cell line microglia 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	gene/protein AGER is_expressed_in tissue/cell line neuron 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	gene/protein AGER, soluble affects_activity of process response to oxidative stress 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	gene/protein AGER, soluble affects_activity of process chronic inflammatory response 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	disease Alzheimer disease decreases_quantity of gene/protein AGER, soluble 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

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
Drugbank DB02533	Aminoguanidine inhibitor NOS2
Drugbank DB02533	Aminoguanidine inhibitor NOS2

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
Drugbank DB02533	Aminoguanidine inhibitor NOS2
Drugbank DB02533	Aminoguanidine inhibitor NOS2

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 disease Alzheimer disease probabely only effective in very early stages of the disease

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 disease Alzheimer disease probabely only effective in very early stages of the disease

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 disease Alzheimer disease probabely only effective in very early stages of the disease

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