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a(CHEBI:"amyloid-beta polypeptide 42")

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Entity

Name
amyloid-beta polypeptide 42
Namespace
chebi
Namespace Version
20180906
Namespace URL
https://raw.githubusercontent.com/pharmacome/terminology/b46b65c3da259b6e86026514dfececab7c22a11b/external/chebi-names.belns

Appears in Networks 24

Amyloid β oligomers (AβOs) in Alzheimer’s disease v1.0.0

albuquerque2009 v1.0.0

This file encodes the article Mammalian Nicotinic Acetylcholine Receptors: From Structure to Function by Albuquerque et al, 2009

Nicotinic acetylcholine receptor signalling: roles in Alzheimer's disease and amyloid neuroprotection. v1.0.0

Nicotinic Acetylcholine Receptors and Nicotinic Cholinergic Mechanisms of the Central Nervous System v1.0.0

Alzheimer's Disease: Targeting the Cholinergic System v1.0.0

M1 muscarinic acetylcholine receptor in Alzheimer’s disease v1.0.0

This file encodes the article M1 muscarinic acetylcholine receptor in Alzheimer’s disease by Jiang et al, 2014

Role of the nicotinic acetylcholine receptor in Alzheimer's disease pathology and treatment v1.0.1

Nuclear receptors as therapeutic targets for Alzheimer's disease. v1.0.0

Cholinergic system during the progression of Alzheimer’s disease: therapeutic implications v1.0.0

Nicotinic receptors: allosteric transitions and therapeutic targets in the nervous system v1.0.0

This document contains the curation of the review article Nicotinic receptors: allosteric transitions and therapeutic targets in the nervous system by Taly et al. 2009

A chaperome subnetwork safeguards proteostasis in aging and neurodegenerative disease. v1.0.0

The Ubiquitin Proteasome System in Neurodegenerative Diseases: Sometimes the Chicken, Sometimes the Egg v1.0.0

Promoting the clearance of neurotoxic proteins in neurodegenerative disorders of ageing v1.0.0

Neuropathogenic role of adenylate kinase-1 in Aβ-mediated tau phosphorylation via AMPK and GSK3β. v1.0.0

Clearance systems in the brain-implications for Alzheimer disease. v1.0.1

Clearance of Amyloid Beta and Tau in Alzheimer’s Disease:from Mechanisms to Therapy v1.0.1

Inflammasome activation and innate immunity in Alzheimer’s disease v1.0.2

Amyloid-Binding Alcohol Dehydrogenase (ABAD) Inhibitors for the Treatment of Alzheimer’s Disease v1.0.0

Anatabine lowers Alzheimer's Aβ production in vitro and in vivo v1.0.0

The Ubiquitin–Proteasome System and the Autophagic–Lysosomal System in Alzheimer Disease v1.0.0

The Spleen Tyrosine Kinase (Syk) Regulates Alzheimer Amyloid-β Production and Tau Hyperphosphorylation* v1.0.0

Phytochemicals as inhibitors of NF-κB for treatment of Alzheimer’s disease v1.0.0

Upstream regulators and downstream effectors of NF-κBinAlzheimer's disease v1.0.0

Significance of NF-κB as a pivotal therapeutic target in the neurodegenerative pathologies of Alzheimer's disease and multiple sclerosis v1.0.0

In-Edges 66

path(MESH:"Alzheimer Disease") negativeCorrelation a(CHEBI:"amyloid-beta polypeptide 42") View Subject | View Object

Despite enhanced Aβ42 accumulation in AD brain (Lewczuk et al. 2003), concentrations of monomeric Aβ42 in the CSF of AD patients are decreased PubMed:29196815

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MeSH
Extracellular Space
Cell Ontology (CL)
neuron
Confidence
High
MeSH
Hippocampus

complex(a(CHEBI:"amyloid-beta polypeptide 42"), p(HGNC:CHRNA7)) hasComponent a(CHEBI:"amyloid-beta polypeptide 42") View Subject | View Object

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act(p(HGNCGENEFAMILY:"Cholinergic receptors nicotinic subunits")) association a(CHEBI:"amyloid-beta polypeptide 42") View Subject | View Object

Other endogenous ligands that impact on the activity of nAChRs noncompetitively and voltage independently include the amyloid beta peptide 1-42 (Abeta1-42; Refs. 123, 376) and the canabinoid anandamide (356, 442). PubMed:19126755

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Text Location
Review

p(HBP:"gamma-secretase") increases a(CHEBI:"amyloid-beta polypeptide 42") View Subject | View Object

The Abeta1-42 peptide is one of the breakdown products of the proteolytic cleavage of the amyloid precursor protein by beta- and gamma-secretases. In biopsy samples of human brain tissue obtained from AD patients and in ectopic systems overexpressing either alpha7 nAChRs or APP, Abeta1-42 coimmunoprecipitates with alpha7 nAChRs (490). The Abeta1-42 peptide also displaces binding of [3H]MLA from alpha7 nAChRs in cerebral cortical and hippocampal synaptosomes (490). PubMed:19126755

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Text Location
Review

p(HGNC:BACE1) increases a(CHEBI:"amyloid-beta polypeptide 42") View Subject | View Object

The Abeta1-42 peptide is one of the breakdown products of the proteolytic cleavage of the amyloid precursor protein by beta- and gamma-secretases. In biopsy samples of human brain tissue obtained from AD patients and in ectopic systems overexpressing either alpha7 nAChRs or APP, Abeta1-42 coimmunoprecipitates with alpha7 nAChRs (490). The Abeta1-42 peptide also displaces binding of [3H]MLA from alpha7 nAChRs in cerebral cortical and hippocampal synaptosomes (490). PubMed:19126755

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Text Location
Review

composite(a(CHEBI:"amyloid-beta polypeptide 40"), a(CHEBI:"amyloid-beta polypeptide 42")) hasComponent a(CHEBI:"amyloid-beta polypeptide 42") View Subject | View Object

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path(MESH:"Alzheimer Disease") association a(CHEBI:"amyloid-beta polypeptide 42") View Subject | View Object

An increasing ratio of the full-length, 1–42 peptide to the 1–40 form is associated with disease (Kumar-Singh et al., 2006), and mutations underlying familial forms of AD either increase this ratio or increase the amount of Abeta secreted. PubMed:19293145

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a(PUBCHEM:10013505) decreases a(CHEBI:"amyloid-beta polypeptide 42") View Subject | View Object

Moreover, the M1 agonist AF267B can rescue the cognitive impairment and decrease Aβ42 and tau abnormalities in the cortex and hippocampus of a mouse model of AD PubMed:26813123

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MeSH
Hippocampus
MeSH
Neocortex
MeSH
Alzheimer Disease

a(CHEBI:cevimeline) decreases a(CHEBI:"amyloid-beta polypeptide 42") View Subject | View Object

Administration of AF267B and AF102B (Cevimeline, EVOXACTM), an M1 mAChRselective agonist once prescribed for the treatment of Sjogren’s syndrome, decreases Abeta42 levels in the cerebral spinal fluid (CSF) of rabbits without affecting APP PubMed:24590577

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MeSH
Cerebrospinal Fluid

a(MESH:"(S)-2-ethyl-8-methyl-1-thia-4,8-diazaspiro(4.5)decan-3-one") decreases a(CHEBI:"amyloid-beta polypeptide 42") View Subject | View Object

Administration of AF267B and AF102B (Cevimeline, EVOXACTM), an M1 mAChRselective agonist once prescribed for the treatment of Sjogren’s syndrome, decreases Abeta42 levels in the cerebral spinal fluid (CSF) of rabbits without affecting APP PubMed:24590577

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MeSH
Cerebrospinal Fluid

a(CHEBI:nicotine) decreases a(CHEBI:"amyloid-beta polypeptide 42") View Subject | View Object

The analysis of the Abeta fraction reduced by nicotine showed that mainly insoluble Ab1-40/42 was affected while there was no change in soluble Abeta (Nordberg et al., 2002) PubMed:25514383

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MeSH
Alzheimer Disease

a(CHEBI:nicotine) decreases a(CHEBI:"amyloid-beta polypeptide 42") View Subject | View Object

The short-term treatment of 10 days showed a significant reduction in cortical insoluble Abeta1-40/42 PubMed:25514383

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MeSH
Alzheimer Disease

complex(a(CHEBI:"amyloid-beta polypeptide 42"), a(MESH:"alpha7 Nicotinic Acetylcholine Receptor")) hasComponent a(CHEBI:"amyloid-beta polypeptide 42") View Subject | View Object

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complex(a(CHEBI:"amyloid-beta polypeptide 42"), p(MGI:Chrna7)) hasComponent a(CHEBI:"amyloid-beta polypeptide 42") View Subject | View Object

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a(CHEBI:pioglitazone) decreases a(CHEBI:"amyloid-beta polypeptide 42") View Subject | View Object

When a higher dose of pioglitazone (7 days/40 mg/kg/day) was used in 10-monthold transgenic mice overexpressing the APP V717I mutation, a 20-- 25% decrease in plaque burden was observed with significant reduction in Ab42 levels within the brains of these animals [61]. PubMed:21718217

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Confidence
High

a(CHEBI:rosiglitazone) decreases a(CHEBI:"amyloid-beta polypeptide 42") View Subject | View Object

Pedersen and Flynn examined the effects of rosiglitazone and found that activation of PPAR-g ameliorated behavioral deficits in the Tg2576 AD mouse model. However, these animals displayed no changes in plaque pathology, but had reduced brain Ab42 levels. PubMed:21718217

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Confidence
High

p(HGNC:APH1A) increases a(CHEBI:"amyloid-beta polypeptide 42") View Subject | View Object

The Ab peptide is generated by the sequential cleavage of the amyloid precursor protein (APP) by the b and g secretases, resulting in the generation of peptides 40 or 42 amino acids in length [2]. PubMed:21718217

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Confidence
Medium

a(MESHC:"(S)-2-ethyl-8-methyl-1-thia-4,8-diazaspiro(4.5)decan-3-one") decreases a(CHEBI:"amyloid-beta polypeptide 42") View Subject | View Object

Recently, a novel group of M1 partial agonists was developed (AF102B, AF150(S) and AF267B-i) [129]. In a series of studies using the 3x transgenic-AD mice, which recapitulate the major pathologies of AD [130], chronic AF267B treatment rescued cognitive impairment and decreased Abeta42 and tau pathologies in the cortex and hippocampus. These changes were associated with M1 mAChR-mediated activation of the TNFalpha-converting enzyme ADAM17/TACE, decreased BACE1 steady state levels and inhibition of GSK3beta [130]. PubMed:18986241

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Disease Ontology (DO)
Alzheimer's disease
MeSH
Cerebral Cortex
MeSH
Hippocampus
MeSH
Cognitive Dysfunction

a(MESH:"3-(2,4-dimethoxybenzylidene)anabaseine") decreases act(a(CHEBI:"amyloid-beta polypeptide 42")) View Subject | View Object

As with nicotine, the weak alpha7 nAChR agonist GTS-21 is neuroprotective, specifically protecting against Abeta1–42-elicited neurotoxicity154. This effect is probably due to small, protracted increases in receptor-mediated Ca2+ influx. importantly, high concentrations of GTS-21 reduced cell survival, underlining the possible risk of over-stimulation152 PubMed:19721446

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Text Location
Review

p(FPLX:"CCT_complex") decreases a(CHEBI:"amyloid-beta polypeptide 42") View Subject | View Object

This functional screen identified 18 genes (Figure 3D), corresponding to ten ATP-dependent chaperones, HSC70 (hsp-1), HSP90 (daf-21), and eight subunits of the CCT/TRiC chaperonin complex; the co-chaperones, HSP40 (dnj-12) and CDC37 (cdc-37); and the TPR-domain pro- tein STI1 that upon knockdown significantly enhanced A b 42 pro- teotoxicity (Figure 3D). PubMed:25437566

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MeSH
Brain
MeSH
Alzheimer Disease
MeSH
Huntington Disease
MeSH
Parkinson Disease

p(FPLX:HSP90) decreases a(CHEBI:"amyloid-beta polypeptide 42") View Subject | View Object

This functional screen identified 18 genes (Figure 3D), corresponding to ten ATP-dependent chaperones, HSC70 (hsp-1), HSP90 (daf-21), and eight subunits of the CCT/TRiC chaperonin complex; the co-chaperones, HSP40 (dnj-12) and CDC37 (cdc-37); and the TPR-domain pro- tein STI1 that upon knockdown significantly enhanced A b 42 pro- teotoxicity (Figure 3D). PubMed:25437566

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MeSH
Brain
MeSH
Alzheimer Disease
MeSH
Huntington Disease
MeSH
Parkinson Disease

p(HGNC:DNAJA1) decreases a(CHEBI:"amyloid-beta polypeptide 42") View Subject | View Object

This functional screen identified 18 genes (Figure 3D), corresponding to ten ATP-dependent chaperones, HSC70 (hsp-1), HSP90 (daf-21), and eight subunits of the CCT/TRiC chaperonin complex; the co-chaperones, HSP40 (dnj-12) and CDC37 (cdc-37); and the TPR-domain pro- tein STI1 that upon knockdown significantly enhanced A b 42 pro- teotoxicity (Figure 3D). PubMed:25437566

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MeSH
Brain
MeSH
Alzheimer Disease
MeSH
Huntington Disease
MeSH
Parkinson Disease

p(HGNC:HSPA8) decreases a(CHEBI:"amyloid-beta polypeptide 42") View Subject | View Object

This functional screen identified 18 genes (Figure 3D), corresponding to ten ATP-dependent chaperones, HSC70 (hsp-1), HSP90 (daf-21), and eight subunits of the CCT/TRiC chaperonin complex; the co-chaperones, HSP40 (dnj-12) and CDC37 (cdc-37); and the TPR-domain pro- tein STI1 that upon knockdown significantly enhanced A b 42 pro- teotoxicity (Figure 3D). PubMed:25437566

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Annotations
MeSH
Brain
MeSH
Alzheimer Disease
MeSH
Huntington Disease
MeSH
Parkinson Disease

p(HGNC:STIP1) decreases a(CHEBI:"amyloid-beta polypeptide 42") View Subject | View Object

This functional screen identified 18 genes (Figure 3D), corresponding to ten ATP-dependent chaperones, HSC70 (hsp-1), HSP90 (daf-21), and eight subunits of the CCT/TRiC chaperonin complex; the co-chaperones, HSP40 (dnj-12) and CDC37 (cdc-37); and the TPR-domain pro- tein STI1 that upon knockdown significantly enhanced A b 42 pro- teotoxicity (Figure 3D). PubMed:25437566

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Annotations
MeSH
Brain
MeSH
Alzheimer Disease
MeSH
Huntington Disease
MeSH
Parkinson Disease

rxn(reactants(p(HGNC:APP)), products(a(CHEBI:"amyloid-beta polypeptide 40"), a(CHEBI:"amyloid-beta polypeptide 42"))) hasProduct a(CHEBI:"amyloid-beta polypeptide 42") View Subject | View Object

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a(CHEBI:"5-chloro-7-iodoquinolin-8-ol") decreases a(CHEBI:"amyloid-beta polypeptide 42") View Subject | View Object

Indeed, clioquinol countered disruption of autophagy by chloroquine in retinal cells, reduced Aβ42 accumulation in CHO cells expressing APP and mutant presenilin 1 and diminished amyloid misfolding and aggregation in Tg2576 AD mice 196,197 . PubMed:30116051

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a(CHEBI:cilostazol) decreases a(CHEBI:"amyloid-beta polypeptide 42") View Subject | View Object

Cilostazol (a phosphodiesterase 3 inhibitor) clears Aβ42 from neuronal cell lines by promoting autophagy, upregulating beclin 1, ATG5 and LC3, downregulating mTORC1 and inducing lysosomal cathepsin B; these actions of cilostazol involve activation of SIRT1 as well as upstream Tyr172 phosphorylation of AMPK 108,162,163 . PubMed:30116051

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MeSH
Dopaminergic Neurons
MeSH
Machado-Joseph Disease

a(CHEBI:cilostazol) decreases a(CHEBI:"amyloid-beta polypeptide 42") View Subject | View Object

Cilostazol improved cognition and reduced levels of Aβ42 and hyperphosphorylated tau following intra- cerebroventricular injection of Aβ25–35 into mice 162,163 . PubMed:30116051

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MeSH
Machado-Joseph Disease

a(CHEBI:resveratrol) decreases a(CHEBI:"amyloid-beta polypeptide 42") View Subject | View Object

Interestingly, resver- atrol downregulated RAGE as well as MMP9 — an effect that is related to decreased hippocampal load of Aβ42 (REF.297) . PubMed:30116051

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MeSH
Hippocampus

a(CHEBI:rifampicin) increases deg(a(CHEBI:"amyloid-beta polypeptide 42")) View Subject | View Object

The antibiotic rifampicin likewise promoted Aβ42 clearance by induc- ing BBB-localized LRP1 and P glycoprotein 1 (REFS273,292) . PubMed:30116051

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a(HBP:HBP00030) increases a(CHEBI:"amyloid-beta polypeptide 42") View Subject | View Object

Third, apolipoprotein E allele 4 (APOE4), a major risk allele for sporadic AD, is associated with increased generation and accumula- tion of Aβ42 (REFS59,60) . PubMed:30116051

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MeSH
Alzheimer Disease

bp(GO:"chaperone-mediated autophagy") causesNoChange deg(a(CHEBI:"amyloid-beta polypeptide 42")) View Subject | View Object

Tau, α-synuclein and TDP43 are substrates for CMA degradation, as are amyloid precursor protein (APP) but not amyloid-β fragment 42 (Aβ42) itself 3,45–47,48 . PubMed:30116051

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p(HGNC:MME) increases deg(a(CHEBI:"amyloid-beta polypeptide 42")) View Subject | View Object

Similar to IDE, neprilysin catabolizes Aβ42, and its loss in mouse models of AD and in patients with AD alike also contributes to Aβ42 accumulation 253,256,260 . PubMed:30116051

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p(HGNC:PLG) increases deg(a(CHEBI:"amyloid-beta polypeptide 42")) View Subject | View Object

Like IDE and neprilysin, plasmin degrades Aβ42 and blocks Aβ42-induced toxicity, suggesting that the decrease in its levels in AD is involved in the evolution of AD 254,256,261 . PubMed:30116051

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p(HGNC:AK1) decreases act(a(CHEBI:"amyloid-beta polypeptide 42")) View Subject | View Object

Compared with control neurons, the effects of Ab42 on tau phosphorylation at CP13, PHF-1 and AT180 epitopes were significantly ameliorated in AK1 knockdown cortical neurons PubMed:22419736

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act(p(HGNC:AK1)) association a(CHEBI:"amyloid-beta polypeptide 42") View Subject | View Object

As shown in Figure 5A and B, treatment of control cells with Ab42 reduced the levels of AMPK phosphorylation at Thr172 and the inhibitory phosphorylation of GSK3b at Ser9. On the contrary, these alterations triggered by Ab42 were not observed in SH-SY5Y/AK1 knockdown cells, showing no changes in the levels of the phosphorylated AMPK and GSK3b. These results suggest that AK1 plays a crucial role in the regulation of AMPK and GSK3b in the neuronal cells exposed to Ab42. PubMed:22419736

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path(MESH:Tauopathies) association a(CHEBI:"amyloid-beta polypeptide 42") View Subject | View Object

A number of studies have found that Ab species, including oligomeric Ab42, are important factors responsible for tau pathogenesis PubMed:22419736

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path(MESH:"Alzheimer Disease") association a(CHEBI:"amyloid-beta polypeptide 42") View Subject | View Object

Given the size of AD-related proteins, mono- meric Aβ1-40, Aβ1-42 and tau, should be able to pass freely through astrocytic endfeet clefts at the glial barrier.72 PubMed:26195256

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a(MESH:"Gastrointestinal Tract") causesNoChange a(CHEBI:"amyloid-beta polypeptide 42") View Subject | View Object

By measuring Aβ levels in superior vena cava and inferior vena cava, it is clear thatAβ levels are getting lower and lower along the direction of the vein blood flow, and the contents of Aβ40 and total Aβ in artery are significantly less than those in vein, suggesting a part of Aβ40 and total Aβ can be cleared by peripheral organs and tissues, such as the liver, kidney, skin, and the gastrointestinal tract, although there is no change in Aβ42 concentrations (Xiang et al. 2015) PubMed:29626319

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MeSH
Arteries

a(MESH:Kidney) causesNoChange a(CHEBI:"amyloid-beta polypeptide 42") View Subject | View Object

By measuring Aβ levels in superior vena cava and inferior vena cava, it is clear thatAβ levels are getting lower and lower along the direction of the vein blood flow, and the contents of Aβ40 and total Aβ in artery are significantly less than those in vein, suggesting a part of Aβ40 and total Aβ can be cleared by peripheral organs and tissues, such as the liver, kidney, skin, and the gastrointestinal tract, although there is no change in Aβ42 concentrations (Xiang et al. 2015) PubMed:29626319

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MeSH
Arteries

a(MESH:Liver) causesNoChange a(CHEBI:"amyloid-beta polypeptide 42") View Subject | View Object

By measuring Aβ levels in superior vena cava and inferior vena cava, it is clear thatAβ levels are getting lower and lower along the direction of the vein blood flow, and the contents of Aβ40 and total Aβ in artery are significantly less than those in vein, suggesting a part of Aβ40 and total Aβ can be cleared by peripheral organs and tissues, such as the liver, kidney, skin, and the gastrointestinal tract, although there is no change in Aβ42 concentrations (Xiang et al. 2015) PubMed:29626319

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MeSH
Arteries

a(MESH:Skin) causesNoChange a(CHEBI:"amyloid-beta polypeptide 42") View Subject | View Object

By measuring Aβ levels in superior vena cava and inferior vena cava, it is clear thatAβ levels are getting lower and lower along the direction of the vein blood flow, and the contents of Aβ40 and total Aβ in artery are significantly less than those in vein, suggesting a part of Aβ40 and total Aβ can be cleared by peripheral organs and tissues, such as the liver, kidney, skin, and the gastrointestinal tract, although there is no change in Aβ42 concentrations (Xiang et al. 2015) PubMed:29626319

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MeSH
Arteries

bp(GO:phagocytosis) increases deg(a(CHEBI:"amyloid-beta polypeptide 42")) View Subject | View Object

In addition, Aβ1–42 can increase the expression of TREM2, a surface signaling receptor in microglia, and the up-regulation of TRME2 can facilitate microglial phagocytosis of Aβ1–42 PubMed:29626319

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act(p(HGNC:TREM2)) increases deg(a(CHEBI:"amyloid-beta polypeptide 42")) View Subject | View Object

In addition, Aβ1–42 can increase the expression of TREM2, a surface signaling receptor in microglia, and the up-regulation of TRME2 can facilitate microglial phagocytosis of Aβ1–42 PubMed:29626319

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act(complex(GO:"NLRP1 inflammasome complex")) increases a(CHEBI:"amyloid-beta polypeptide 42") View Subject | View Object

Recently, Kaushal et al. described the involvement of NLRP1 inflammasome activation in neurons. In these experiments, serum deprivation induced NLRP1-dependent caspase-1 activity and ASC speck formation, which resulted in caspase-6 activation and an increase in the Ab42/total Ab ratio (11) PubMed:28019679

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Confidence
High
NeuroMMSigDB
Amyloidogenic subgraph

rxn(reactants(p(HGNC:APP)), products(a(CHEBI:"amyloid-beta polypeptide 42"), p(HBP:"APP C-terminally truncated carboxyl-terminal fragments"))) hasProduct a(CHEBI:"amyloid-beta polypeptide 42") View Subject | View Object

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a(CHEBI:Anatabine) decreases a(CHEBI:"amyloid-beta polypeptide 42") View Subject | View Object

Anatabine dose dependently inhibited Aβ1–40 and Aβ1–42 with an approximate half maximal inhibitory concentration of 640 μg/ml for both Aβ1–40 and Aβ1–42 (Fig. 2). PubMed:21958873

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Experimental Factor Ontology (EFO)
CHO cell

a(CHEBI:Anatabine) decreases a(CHEBI:"amyloid-beta polypeptide 42") View Subject | View Object

We then tested the impact of anatabine on sAPPα and sAPPβ production using 7W CHO cells and observed that anatabine inhibits sAPPβ secretion without impacting sAPPα suggesting that anatabine is preventing the β-cleavage of APP (Fig. 4). PubMed:21958873

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Experimental Factor Ontology (EFO)
CHO cell

a(CHEBI:Anatabine) decreases a(CHEBI:"amyloid-beta polypeptide 42") View Subject | View Object

A significant reduction in the accumulation of brain soluble and insoluble Aβ1–40 and Aβ1–42 was observed following four days of treatment with 2 mg/kg of anatabine (Fig. 9). PubMed:21958873

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MeSH
Brain

a(CHEBI:"amyloid-beta") positiveCorrelation a(CHEBI:"amyloid-beta polypeptide 42") View Subject | View Object

Consistent with these findings, strong overexpression of human Ab42, but not Ab40, in Drosophila neurons induces age-related accumulation of Ab in autolysosomes and neurotoxicity (Ling et al. 2009). PubMed:22908190

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MeSH
Neurons

a(CHEBI:"low-density lipoprotein cholesterol") positiveCorrelation tloc(a(CHEBI:"amyloid-beta polypeptide 42"), fromLoc(GO:cytosol), toLoc(GO:lysosome)) View Subject | View Object

By up-regulating endocytosis, high dietary LDL-cholesterol and overexpression of its receptor ApoE (particularly ApoE 14) elevate bCTF levels and increase delivery of Ab1–42 to lysosomes in cellular model systems (Ji et al. 2006; Cossec et al. 2010). PubMed:22908190

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bp(GO:endocytosis) positiveCorrelation tloc(a(CHEBI:"amyloid-beta polypeptide 42"), fromLoc(GO:cytosol), toLoc(GO:lysosome)) View Subject | View Object

By up-regulating endocytosis, high dietary LDL-cholesterol and overexpression of its receptor ApoE (particularly ApoE 14) elevate bCTF levels and increase delivery of Ab1–42 to lysosomes in cellular model systems (Ji et al. 2006; Cossec et al. 2010). PubMed:22908190

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g(HBP:"APOE e4") positiveCorrelation tloc(a(CHEBI:"amyloid-beta polypeptide 42"), fromLoc(GO:cytosol), toLoc(GO:lysosome)) View Subject | View Object

By up-regulating endocytosis, high dietary LDL-cholesterol and overexpression of its receptor ApoE (particularly ApoE 14) elevate bCTF levels and increase delivery of Ab1–42 to lysosomes in cellular model systems (Ji et al. 2006; Cossec et al. 2010). PubMed:22908190

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path(HBP:neurotoxicity) positiveCorrelation a(CHEBI:"amyloid-beta polypeptide 42") View Subject | View Object

Consistent with these findings, strong overexpression of human Ab42, but not Ab40, in Drosophila neurons induces age-related accumulation of Ab in autolysosomes and neurotoxicity (Ling et al. 2009). PubMed:22908190

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MeSH
Neurons

a(CHEBI:"2-[[7-(3,4-dimethoxyphenyl)-5-imidazo[1,2-c]pyrimidinyl]amino]-3-pyridinecarboxamide") decreases a(CHEBI:"amyloid-beta polypeptide 42") View Subject | View Object

We observed that BAY61-3606 significantly reduces brain Aβ38, Aβ40, and Aβ42 levels in Tg PS1/ APPsw mice (Fig. 7, C and D). PubMed:25331948

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MeSH
Brain

a(CHEBI:"2-[[7-(3,4-dimethoxyphenyl)-5-imidazo[1,2-c]pyrimidinyl]amino]-3-pyridinecarboxamide") increases tloc(a(CHEBI:"amyloid-beta polypeptide 42"), fromLoc(GO:intracellular), toLoc(MESH:Plasma)) View Subject | View Object

In addition, we found that BAY61-3606 stimulates the clearance of Aβ across the BBB in wild-type mice as demonstrated by increased circulating plasma levels of human Aβ42 in mice treated with the Syk inhibitor compared with vehicle-treated mice following the intracranial injection of human Aβ42 (Fig. 7B) PubMed:25331948

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MeSH
Blood-Brain Barrier

a(CHEBI:Nilvadipine) decreases a(CHEBI:"amyloid-beta polypeptide 42") View Subject | View Object

We found that both the (-)- and (+)-nilvadipine enantiomers enhance Aβ42 clearance from the brain to the peripheral side of the in vitro BBB model (Fig. 2A). PubMed:25331948

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MeSH
Brain

a(CHEBI:Nilvadipine) increases tloc(a(CHEBI:"amyloid-beta polypeptide 42"), fromLoc(GO:intracellular), toLoc(MESH:Plasma)) View Subject | View Object

Data show that (-)-nilvadipine stimulated the clearance of human Aβ42 across the BBB as more human Aβ42 was detected in the plasma of (-)-nilvadipine-treated mice than control animals (Fig. 2B). PubMed:25331948

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MeSH
Blood-Brain Barrier

a(CHEBI:"N(5)-ethyl-L-glutamine") decreases a(CHEBI:"amyloid-beta polypeptide 42") View Subject | View Object

Moreover, the level of A 1-42 was lowered by L-theanine and caused A 1-42- activated neuronal cell death in the cortex and hip-pocampus of the brain [128]. PubMed:29179999

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a(CHEBI:Anatabine) decreases a(CHEBI:"amyloid-beta polypeptide 42") View Subject | View Object

It con-siderably lowered the expression of A 1-40 and A 1-42 in an AD transgenic mouse [195]. PubMed:29179999

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MeSH
Alzheimer Disease

a(PUBCHEM:155160) decreases a(CHEBI:"amyloid-beta polypeptide 42") View Subject | View Object

LPS-stimulated memory impairments were improved by 4-O-methylhonokinol through the inhibition of A 1-42 expression. PubMed:29179999

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a(PUBCHEM:45270574) decreases act(a(CHEBI:"amyloid-beta polypeptide 42")) View Subject | View Object

ICV infusion of impairments by A 1-42 was considerably reduced with the treatment of obovatol [161]. PubMed:29179999

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a(CHEBI:nicorandil) decreases a(CHEBI:"amyloid-beta polypeptide 42") View Subject | View Object

Nicorandil, ATP-sensitive potassium channel opener, reduced apo- ptosis and decreased oxidative stress, downregulated APP695 mRNA and APP695 protein expression, also reduced Aβ 42 levels in the medium [90]. PubMed:27288790

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MeSH
Cerebral Cortex
MeSH
Hippocampus

a(PUBCHEM:439378) decreases a(CHEBI:"amyloid-beta polypeptide 42") View Subject | View Object

L-Theanine, an amino acid in green tea, reduced Aβ 42 levels in the cortex and hippocampus of the brain, which is mediated by suppres- sion of ERK/p38 and NF-κB as well as the reduction of macromolecular oxidative damage [81]. PubMed:27288790

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MeSH
Cerebral Cortex
MeSH
Hippocampus

r(HGNC:"BACE1-AS") increases a(CHEBI:"amyloid-beta polypeptide 42") View Subject | View Object

Upon exposure to various cell stressors including Aβ 42 , expression of BACE1-AS becomes elevated, increasing BACE1 mRNA stability and generating additional Aβ 42 through a post-transcriptional feed-forward mechanism [74]. PubMed:27288790

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act(a(MESH:Microglia)) positiveCorrelation a(CHEBI:"amyloid-beta polypeptide 42") View Subject | View Object

Excessive accumulation of Aβ1-42 stimulates microglial cells by signaling via receptor associated advanced glycation end products (RAGE) and peroxisome proliferator-activated receptor-γ (PPAR-γ), phosphorylates IKK proteins, and enhances NF-κB mediated transactivation of inflammatory cytokines and neurotoxic molecules such as glutamate and reactive oxygen species (ROS)/induced nitric oxide synthase (iNOS) [12] (Fig 2B) PubMed:25652642

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MeSH
Alzheimer Disease

Out-Edges 72

a(CHEBI:"amyloid-beta polypeptide 42") negativeCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

Despite enhanced Aβ42 accumulation in AD brain (Lewczuk et al. 2003), concentrations of monomeric Aβ42 in the CSF of AD patients are decreased PubMed:29196815

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MeSH
Extracellular Space
Cell Ontology (CL)
neuron
Confidence
High
MeSH
Hippocampus

a(CHEBI:"amyloid-beta polypeptide 42") decreases act(p(HBP:"alpha-4 beta-2 nAChR")) View Subject | View Object

Other studies have reported that alpha4beta2 nAChRs are more sensitive than alpha7 nAChRs to inhibition by nanomolar concentrations of Abeta1-42 (506). PubMed:19126755

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Text Location
Review

a(CHEBI:"amyloid-beta polypeptide 42") association act(p(HGNCGENEFAMILY:"Cholinergic receptors nicotinic subunits")) View Subject | View Object

Other endogenous ligands that impact on the activity of nAChRs noncompetitively and voltage independently include the amyloid beta peptide 1-42 (Abeta1-42; Refs. 123, 376) and the canabinoid anandamide (356, 442). PubMed:19126755

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a(CHEBI:"amyloid-beta polypeptide 42") regulates act(p(HGNCGENEFAMILY:"Cholinergic receptors nicotinic subunits")) View Subject | View Object

It is noteworthy that the alpha7 nAChR activity increases intracellular accumulation of Abeta in neurons (336), and Abeta peptides, in addition to modulating nAChR activity, downregulate the expression of nAChRs (197). PubMed:19126755

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MeSH
Neurons
Text Location
Review

a(CHEBI:"amyloid-beta polypeptide 42") increases complex(a(CHEBI:"amyloid-beta polypeptide 42"), p(HGNC:CHRNA7)) View Subject | View Object

The Abeta1-42 peptide is one of the breakdown products of the proteolytic cleavage of the amyloid precursor protein by beta- and gamma-secretases. In biopsy samples of human brain tissue obtained from AD patients and in ectopic systems overexpressing either alpha7 nAChRs or APP, Abeta1-42 coimmunoprecipitates with alpha7 nAChRs (490). The Abeta1-42 peptide also displaces binding of [3H]MLA from alpha7 nAChRs in cerebral cortical and hippocampal synaptosomes (490). PubMed:19126755

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MeSH
Brain
MeSH
Alzheimer Disease
Text Location
Review

a(CHEBI:"amyloid-beta polypeptide 42") decreases complex(a(MESH:methyllycaconitine), p(HGNC:CHRNA7)) View Subject | View Object

The Abeta1-42 peptide is one of the breakdown products of the proteolytic cleavage of the amyloid precursor protein by beta- and gamma-secretases. In biopsy samples of human brain tissue obtained from AD patients and in ectopic systems overexpressing either alpha7 nAChRs or APP, Abeta1-42 coimmunoprecipitates with alpha7 nAChRs (490). The Abeta1-42 peptide also displaces binding of [3H]MLA from alpha7 nAChRs in cerebral cortical and hippocampal synaptosomes (490). PubMed:19126755

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MeSH
Brain
MeSH
Alzheimer Disease
Text Location
Review

a(CHEBI:"amyloid-beta polypeptide 42") decreases act(p(HGNC:CHRNA7)) View Subject | View Object

More functional studies reported that while at picomolar concentrations Abeta1-42 activates alpha7 nAChRs ectopically expressed in Xenopus oocytes (123, 126), at nanomolar concentrations it inhibits alpha7 nAChRs present in different preparations (278, 376). The alpha7 nAChR inhibition by Abeta1-42 is noncompetitive with respect to the agonist, is voltage independent, and is therefore likely to be mediated by the interaction of the peptide with a site different from that for ACh on the nAChRs. PubMed:19126755

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Review

a(CHEBI:"amyloid-beta polypeptide 42") decreases r(HGNCGENEFAMILY:"Cholinergic receptors nicotinic subunits") View Subject | View Object

It is noteworthy that the alpha7 nAChR activity increases intracellular accumulation of Abeta in neurons (336), and Abeta peptides, in addition to modulating nAChR activity, downregulate the expression of nAChRs (197). PubMed:19126755

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MeSH
Neurons
Text Location
Review

a(CHEBI:"amyloid-beta polypeptide 42") association path(MESH:"Alzheimer Disease") View Subject | View Object

An increasing ratio of the full-length, 1–42 peptide to the 1–40 form is associated with disease (Kumar-Singh et al., 2006), and mutations underlying familial forms of AD either increase this ratio or increase the amount of Abeta secreted. PubMed:19293145

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a(CHEBI:"amyloid-beta polypeptide 42") increases act(p(HGNCGENEFAMILY:"Cholinergic receptors nicotinic subunits")) View Subject | View Object

Abeta1–42 activates heterologously expressed nAChRs (Dineley et al., 2002), and Abeta25–35 has been shown to activate non-alpha7 nAChRs in rat basal forebrain neurons (Fu and Jhamandas, 2003) and to evoke a alpha7- mediated calcium increases in presynaptic terminals isolated from rat hippocampus and neocortex (Dougherty et al., 2003). PubMed:19293145

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a(CHEBI:"amyloid-beta polypeptide 42") decreases act(p(FPLX:CHRN)) View Subject | View Object

With the use of selective antagonists it was possible to determine that inhibition operates on both alpha7 and non-alpha7 receptors (Pettit et al., 2001) PubMed:25514383

Appears in Networks:

a(CHEBI:"amyloid-beta polypeptide 42") decreases bp(MESH:"Synaptic Potentials") View Subject | View Object

Modulation of nAChRs by Abeta was also found in ex vivo studies: Pettit and colleagues (2001) used rat hippocampal slices to show that Abeta1-42 incubation is able to reduce postsynaptic currents and open probability of both alpha7 and non-alpha7 nAChRs subtypes, demonstrating an interaction between Abeta and other nAChR subunits PubMed:25514383

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a(CHEBI:"amyloid-beta polypeptide 42") decreases bp(MESH:"Synaptic Potentials") View Subject | View Object

They demonstrated that Abeta1-42 drives a reversible inhibition of nAChR-mediated currents in hippocampal GABAergic neurons recorded from rat slices. In these experimental conditions the most effective Abeta1-42 concentration was 500 nM, but inhibition was found also at the lower concentration of 100 nM PubMed:25514383

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Cell Ontology (CL)
GABAergic neuron
MeSH
Hippocampus

a(CHEBI:"amyloid-beta polypeptide 42") decreases act(p(FPLX:CHRN)) View Subject | View Object

They demonstrated that Abeta1-42 drives a reversible inhibition of nAChR-mediated currents in hippocampal GABAergic neurons recorded from rat slices. In these experimental conditions the most effective Abeta1-42 concentration was 500 nM, but inhibition was found also at the lower concentration of 100 nM PubMed:25514383

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Cell Ontology (CL)
GABAergic neuron
MeSH
Hippocampus

a(CHEBI:"amyloid-beta polypeptide 42") decreases act(a(MESH:"alpha7 Nicotinic Acetylcholine Receptor")) View Subject | View Object

With the use of selective antagonists it was possible to determine that inhibition operates on both alpha7 and non-alpha7 receptors (Pettit et al., 2001) PubMed:25514383

Appears in Networks:

a(CHEBI:"amyloid-beta polypeptide 42") decreases act(a(MESH:"alpha7 Nicotinic Acetylcholine Receptor")) View Subject | View Object

The incubation of cultured rat hippocampal neurons with Abeta1-42 resulted in inhibition of alpha7 nAChRs, more precisely of both somato-dendritic and presynaptic populations of receptors PubMed:25514383

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MeSH
Hippocampus
MeSH
Neurons

a(CHEBI:"amyloid-beta polypeptide 42") decreases act(a(HBP:"alpha-4 beta-2 nAChR")) View Subject | View Object

Further studies showed an inhibitory effect of Abeta1-42 on human alpha4beta2 nAChRs transfected in the cell line (SHEP1) (Wu et al., 2004) PubMed:25514383

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a(CHEBI:"amyloid-beta polypeptide 42") increases bp(GO:"long-term synaptic potentiation") View Subject | View Object

Subsequent to incubation with pM concentrations of Abeta1-42 monomers and oligomers, an increase of hippocampal LTP was observed PubMed:25514383

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a(CHEBI:"amyloid-beta polypeptide 42") increases path(HBP:neurotoxicity) View Subject | View Object

As with nicotine, the weak alpha7 nAChR agonist GTS-21 is neuroprotective, specifically protecting against Abeta1–42-elicited neurotoxicity154. This effect is probably due to small, protracted increases in receptor-mediated Ca2+ influx. importantly, high concentrations of GTS-21 reduced cell survival, underlining the possible risk of over-stimulation152 PubMed:19721446

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Review

a(CHEBI:"amyloid-beta polypeptide 42") increases path(HBP:neurotoxicity) View Subject | View Object

Regardless of the exact effect of Abeta1–42 on receptor activity, it does seem to block the activation by nicotine and, consistent with the cytoprotective nature of this interaction, amyloid deposition limits neuroprotection151. This phenomenon may explain at least part of the neurotoxicity that is associated with Abeta1–42 (ReF. 156). PubMed:19721446

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Review

a(CHEBI:"amyloid-beta polypeptide 42") decreases act(a(CHEBI:nicotine)) View Subject | View Object

Regardless of the exact effect of Abeta1–42 on receptor activity, it does seem to block the activation by nicotine and, consistent with the cytoprotective nature of this interaction, amyloid deposition limits neuroprotection151. This phenomenon may explain at least part of the neurotoxicity that is associated with Abeta1–42 (ReF. 156). PubMed:19721446

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Text Location
Review

a(CHEBI:"amyloid-beta polypeptide 42") decreases bp(MESH:Neuroprotection) View Subject | View Object

Regardless of the exact effect of Abeta1–42 on receptor activity, it does seem to block the activation by nicotine and, consistent with the cytoprotective nature of this interaction, amyloid deposition limits neuroprotection151. This phenomenon may explain at least part of the neurotoxicity that is associated with Abeta1–42 (ReF. 156). PubMed:19721446

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Text Location
Review

a(CHEBI:"amyloid-beta polypeptide 42") increases a(HBP:"amyloid-beta fibrils") View Subject | View Object

Concomitant cleavage of APP by beta and gamma secretase at specific sites can result in fragments (Abeta1-40 or Abeta1-42) that can misfold and form extracellular fibrils. PubMed:14556719

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a(CHEBI:"amyloid-beta polypeptide 42") decreases p(HGNC:IDE) View Subject | View Object

In a vicious circle, Aβ42 itself decreases IDE expression, although it may prompt its release from glia 254,259 . PubMed:30116051

Appears in Networks:

a(CHEBI:"amyloid-beta polypeptide 42") decreases act(p(FPLX:AMPK)) View Subject | View Object

Sixth, Aβ42 compro- mises the function of AMPK to impede initiation of the ALN 67 . PubMed:30116051

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

a(CHEBI:"amyloid-beta polypeptide 42") decreases bp(GO:"autophagosome assembly") View Subject | View Object

Sixth, Aβ42 compro- mises the function of AMPK to impede initiation of the ALN 67 . PubMed:30116051

Appears in Networks:
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MeSH
Alzheimer Disease

a(CHEBI:"amyloid-beta polypeptide 42") decreases bp(GO:"proteasome-mediated ubiquitin-dependent protein catabolic process") View Subject | View Object

Seventh, Aβ42 obstructs the UPS and CMA 47,68 . PubMed:30116051

Appears in Networks:
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MeSH
Alzheimer Disease

a(CHEBI:"amyloid-beta polypeptide 42") decreases bp(GO:"chaperone-mediated autophagy") View Subject | View Object

Seventh, Aβ42 obstructs the UPS and CMA 47,68 . PubMed:30116051

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

a(CHEBI:"amyloid-beta polypeptide 42") decreases bp(GO:"chaperone-mediated autophagy") View Subject | View Object

The UPS and CMA are disrupted by neurotoxic proteins like Aβ42 and tau, hence, their early and preventive reinforcement prior to Aβ42 and tau accumulation may be critical. PubMed:30116051

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a(CHEBI:"amyloid-beta polypeptide 42") decreases a(GO:microtubule) View Subject | View Object

The microtubule stabilizers paclitaxel and epothilone A countered Aβ42-induced cytoskeletal disruption — and moderated excessive UPR — in neurons 182 . PubMed:30116051

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MeSH
Machado-Joseph Disease

a(CHEBI:"amyloid-beta polypeptide 42") increases p(HGNC:AK1) View Subject | View Object

Neuronal expression of AK1 is upregulated in AD patients and is induced by Ab42 PubMed:22419736

Appears in Networks:

a(CHEBI:"amyloid-beta polypeptide 42") regulates p(HGNC:AK1) View Subject | View Object

Therefore, we examined whether oligomeric forms of Ab42 could regulate AK1 expression in neuronal cells. PubMed:22419736

Appears in Networks:

a(CHEBI:"amyloid-beta polypeptide 42") increases p(HGNC:AK1) View Subject | View Object

From western blot analysis, we found that AK1 expression increased 􏰍2-fold in the cortical neurons after exposure to Ab42 PubMed:22419736

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a(CHEBI:"amyloid-beta polypeptide 42") association act(p(HGNC:AK1)) View Subject | View Object

As shown in Figure 5A and B, treatment of control cells with Ab42 reduced the levels of AMPK phosphorylation at Thr172 and the inhibitory phosphorylation of GSK3b at Ser9. On the contrary, these alterations triggered by Ab42 were not observed in SH-SY5Y/AK1 knockdown cells, showing no changes in the levels of the phosphorylated AMPK and GSK3b. These results suggest that AK1 plays a crucial role in the regulation of AMPK and GSK3b in the neuronal cells exposed to Ab42. PubMed:22419736

Appears in Networks:

a(CHEBI:"amyloid-beta polypeptide 42") association path(MESH:Tauopathies) View Subject | View Object

A number of studies have found that Ab species, including oligomeric Ab42, are important factors responsible for tau pathogenesis PubMed:22419736

Appears in Networks:

a(CHEBI:"amyloid-beta polypeptide 42") increases p(HGNC:MAPT, pmod(Ph, Ser, 202)) View Subject | View Object

Interestingly, tau phosphor- ylation, which was detected by PHF-1 (Ser 396/404), CP13 (Ser 202) and 12E8 (Ser 262) antibodies, was also increased by Ab42 PubMed:22419736

Appears in Networks:

a(CHEBI:"amyloid-beta polypeptide 42") increases p(HGNC:MAPT, pmod(Ph, Ser, 396)) View Subject | View Object

Interestingly, tau phosphor- ylation, which was detected by PHF-1 (Ser 396/404), CP13 (Ser 202) and 12E8 (Ser 262) antibodies, was also increased by Ab42 PubMed:22419736

Appears in Networks:

a(CHEBI:"amyloid-beta polypeptide 42") increases p(HGNC:MAPT, pmod(Ph, Ser, 404)) View Subject | View Object

Interestingly, tau phosphor- ylation, which was detected by PHF-1 (Ser 396/404), CP13 (Ser 202) and 12E8 (Ser 262) antibodies, was also increased by Ab42 PubMed:22419736

Appears in Networks:

a(CHEBI:"amyloid-beta polypeptide 42") increases p(HGNC:MAPT, pmod(Ph, Ser, 262)) View Subject | View Object

Interestingly, tau phosphor- ylation, which was detected by PHF-1 (Ser 396/404), CP13 (Ser 202) and 12E8 (Ser 262) antibodies, was also increased by Ab42 PubMed:22419736

Appears in Networks:

a(CHEBI:"amyloid-beta polypeptide 42") causesNoChange p(HGNC:AK3) View Subject | View Object

Among AK isoforms, AK2 was not detected in the primary neurons and HT22 cells, whereas AK3 expression was observed in the neurons but not regulated by Ab42 PubMed:22419736

Appears in Networks:

a(CHEBI:"amyloid-beta polypeptide 42") increases r(HGNC:AK1) View Subject | View Object

When analyzed by reverse transcription-polymerase chain reaction, the level of AK1 mRNA, not AK1b mRNA, increased by Ab42 in primary neurons PubMed:22419736

Appears in Networks:

a(CHEBI:"amyloid-beta polypeptide 42") increases p(HGNC:MAPT, pmod(Ph)) View Subject | View Object

Compared with control neurons, the effects of Ab42 on tau phosphorylation at CP13, PHF-1 and AT180 epitopes were significantly ameliorated in AK1 knockdown cortical neurons PubMed:22419736

Appears in Networks:

a(CHEBI:"amyloid-beta polypeptide 42") decreases p(ECCODE:"2.7.11.31", pmod(Ph, Thr, 171)) View Subject | View Object

Interestingly, treatment with Ab42 decreased the phosphorylation of AMPK at Thr172, whereas the total amount of AMPK was not altered in primary cortical neurons PubMed:22419736

Appears in Networks:

a(CHEBI:"amyloid-beta polypeptide 42") causesNoChange p(ECCODE:"2.7.11.31") View Subject | View Object

Interestingly, treatment with Ab42 decreased the phosphorylation of AMPK at Thr172, whereas the total amount of AMPK was not altered in primary cortical neurons PubMed:22419736

Appears in Networks:

a(CHEBI:"amyloid-beta polypeptide 42") decreases act(p(ECCODE:"2.7.11.31")) View Subject | View Object

We found, in addition, that enzyme activity of AMPK was sup- pressed in the cortical neurons after exposure to Ab42 PubMed:22419736

Appears in Networks:

a(CHEBI:"amyloid-beta polypeptide 42") decreases act(p(ECCODE:"2.7.11.31")) View Subject | View Object

These results indicate that AMPK activity is impaired by Ab42 in the neuronal cells in which tau phosphor- ylation increased. PubMed:22419736

Appears in Networks:

a(CHEBI:"amyloid-beta polypeptide 42") decreases p(MESH:"Acetyl-CoA Carboxylase", pmod(Ph)) View Subject | View Object

Consistently, the phosphorylation of acetyl Co-A carboxylase, a well-defined downstream substrate of AMPK, was also reduced by Ab42 PubMed:22419736

Appears in Networks:

a(CHEBI:"amyloid-beta polypeptide 42") association path(MESH:"Alzheimer Disease") View Subject | View Object

Given the size of AD-related proteins, mono- meric Aβ1-40, Aβ1-42 and tau, should be able to pass freely through astrocytic endfeet clefts at the glial barrier.72 PubMed:26195256

Appears in Networks:

a(CHEBI:"amyloid-beta polypeptide 42") isA a(CHEBI:"amyloid-beta") View Subject | View Object

Appears in Networks:

a(CHEBI:"amyloid-beta polypeptide 42") increases p(HGNC:TREM2) View Subject | View Object

In addition, Aβ1–42 can increase the expression of TREM2, a surface signaling receptor in microglia, and the up-regulation of TRME2 can facilitate microglial phagocytosis of Aβ1–42 PubMed:29626319

Appears in Networks:

tloc(a(CHEBI:"amyloid-beta polypeptide 42"), fromLoc(GO:cytosol), toLoc(GO:lysosome)) positiveCorrelation bp(GO:endocytosis) View Subject | View Object

By up-regulating endocytosis, high dietary LDL-cholesterol and overexpression of its receptor ApoE (particularly ApoE 14) elevate bCTF levels and increase delivery of Ab1–42 to lysosomes in cellular model systems (Ji et al. 2006; Cossec et al. 2010). PubMed:22908190

Appears in Networks:

tloc(a(CHEBI:"amyloid-beta polypeptide 42"), fromLoc(GO:cytosol), toLoc(GO:lysosome)) positiveCorrelation g(HBP:"APOE e4") View Subject | View Object

By up-regulating endocytosis, high dietary LDL-cholesterol and overexpression of its receptor ApoE (particularly ApoE 14) elevate bCTF levels and increase delivery of Ab1–42 to lysosomes in cellular model systems (Ji et al. 2006; Cossec et al. 2010). PubMed:22908190

Appears in Networks:

tloc(a(CHEBI:"amyloid-beta polypeptide 42"), fromLoc(GO:cytosol), toLoc(GO:lysosome)) positiveCorrelation a(CHEBI:"low-density lipoprotein cholesterol") View Subject | View Object

By up-regulating endocytosis, high dietary LDL-cholesterol and overexpression of its receptor ApoE (particularly ApoE 14) elevate bCTF levels and increase delivery of Ab1–42 to lysosomes in cellular model systems (Ji et al. 2006; Cossec et al. 2010). PubMed:22908190

Appears in Networks:

a(CHEBI:"amyloid-beta polypeptide 42") positiveCorrelation a(CHEBI:"amyloid-beta") View Subject | View Object

Consistent with these findings, strong overexpression of human Ab42, but not Ab40, in Drosophila neurons induces age-related accumulation of Ab in autolysosomes and neurotoxicity (Ling et al. 2009). PubMed:22908190

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MeSH
Neurons

a(CHEBI:"amyloid-beta polypeptide 42") positiveCorrelation path(HBP:neurotoxicity) View Subject | View Object

Consistent with these findings, strong overexpression of human Ab42, but not Ab40, in Drosophila neurons induces age-related accumulation of Ab in autolysosomes and neurotoxicity (Ling et al. 2009). PubMed:22908190

Appears in Networks:
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MeSH
Neurons

a(CHEBI:"amyloid-beta polypeptide 42") increases path(HBP:neurotoxicity) View Subject | View Object

Ab42-induced neurotoxicity is further enhanced by autophagy activation and is partially rescued by autophagy inhibition. PubMed:22908190

Appears in Networks:

a(CHEBI:"amyloid-beta polypeptide 42") increases bp(GO:"neuron death") View Subject | View Object

Moreover, the level of A 1-42 was lowered by L-theanine and caused A 1-42- activated neuronal cell death in the cortex and hip-pocampus of the brain [128]. PubMed:29179999

Appears in Networks:
Annotations
MeSH
Cerebral Cortex
MeSH
Hippocampus

a(CHEBI:"amyloid-beta polypeptide 42") increases p(FPLX:IKB, pmod(Ph, Ser, 32)) View Subject | View Object

Results have shown a sig- nificant increase in phosphorylation of IκB at serine 32–36 and NF-κB at serine 536 with Aβ 42 exposure, this phosphorylation enhances p65 transactivation potential [16]. PubMed:27288790

Appears in Networks:

a(CHEBI:"amyloid-beta polypeptide 42") increases p(FPLX:IKB, pmod(Ph, Ser, 36)) View Subject | View Object

Results have shown a sig- nificant increase in phosphorylation of IκB at serine 32–36 and NF-κB at serine 536 with Aβ 42 exposure, this phosphorylation enhances p65 transactivation potential [16]. PubMed:27288790

Appears in Networks:

a(CHEBI:"amyloid-beta polypeptide 42") increases p(FPLX:NFkappaB, pmod(Ph, Ser, 536)) View Subject | View Object

Results have shown a sig- nificant increase in phosphorylation of IκB at serine 32–36 and NF-κB at serine 536 with Aβ 42 exposure, this phosphorylation enhances p65 transactivation potential [16]. PubMed:27288790

Appears in Networks:

a(CHEBI:"amyloid-beta polypeptide 42") increases p(HGNC:BACE1) View Subject | View Object

Aβ 42 mediated increase in BACE1 expression is accompanied by a decrease in Uch-L1 expression and activity in dif- ferent cellular models and in sporadic AD brains, which interferes with the lysosomal degradation of BACE1 [52,56]. PubMed:27288790

Appears in Networks:

a(CHEBI:"amyloid-beta polypeptide 42") increases r(HGNC:"BACE1-AS") View Subject | View Object

Upon exposure to various cell stressors including Aβ 42 , expression of BACE1-AS becomes elevated, increasing BACE1 mRNA stability and generating additional Aβ 42 through a post-transcriptional feed-forward mechanism [74]. PubMed:27288790

Appears in Networks:

a(CHEBI:"amyloid-beta polypeptide 42") regulates p(HGNC:APP) View Subject | View Object

In neuronal cells Aβ1-42 peptide has been shown to regulate APP and BACE1 proteins in NF-κB dependent manner PubMed:25652642

Appears in Networks:
Annotations
MeSH
Neurons
MeSH
Alzheimer Disease

a(CHEBI:"amyloid-beta polypeptide 42") regulates p(HGNC:BACE1) View Subject | View Object

In neuronal cells Aβ1-42 peptide has been shown to regulate APP and BACE1 proteins in NF-κB dependent manner PubMed:25652642

Appears in Networks:
Annotations
MeSH
Neurons
MeSH
Alzheimer Disease

a(CHEBI:"amyloid-beta polypeptide 42") increases act(complex(GO:"NF-kappaB complex")) View Subject | View Object

In neuronal cells Aβ1-42 peptide has been shown to regulate APP and BACE1 proteins in NF-κB dependent manner PubMed:25652642

Appears in Networks:
Annotations
MeSH
Neurons
MeSH
Alzheimer Disease

a(CHEBI:"amyloid-beta polypeptide 42") increases act(complex(GO:"NF-kappaB complex")) View Subject | View Object

Excessive accumulation of Aβ1-42 stimulates microglial cells by signaling via receptor associated advanced glycation end products (RAGE) and peroxisome proliferator-activated receptor-γ (PPAR-γ), phosphorylates IKK proteins, and enhances NF-κB mediated transactivation of inflammatory cytokines and neurotoxic molecules such as glutamate and reactive oxygen species (ROS)/induced nitric oxide synthase (iNOS) [12] (Fig 2B) PubMed:25652642

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

a(CHEBI:"amyloid-beta polypeptide 42") increases complex(p(HGNC:NFKB1), p(HGNC:RELA)) View Subject | View Object

Exposure of primary neuronal cells or post-mitotic neurons to Aβ1-42 peptide has been shown to strongly activate the p50:p65 dimers and mediate neuronal cell death (Fig 1) PubMed:25652642

Appears in Networks:
Annotations
MeSH
Neurons
MeSH
Alzheimer Disease

a(CHEBI:"amyloid-beta polypeptide 42") regulates bp(GO:"cell death") View Subject | View Object

Exposure of primary neuronal cells or post-mitotic neurons to Aβ1-42 peptide has been shown to strongly activate the p50:p65 dimers and mediate neuronal cell death (Fig 1) PubMed:25652642

Appears in Networks:
Annotations
MeSH
Neurons
MeSH
Alzheimer Disease

a(CHEBI:"amyloid-beta polypeptide 42") positiveCorrelation act(a(MESH:Microglia)) View Subject | View Object

Excessive accumulation of Aβ1-42 stimulates microglial cells by signaling via receptor associated advanced glycation end products (RAGE) and peroxisome proliferator-activated receptor-γ (PPAR-γ), phosphorylates IKK proteins, and enhances NF-κB mediated transactivation of inflammatory cytokines and neurotoxic molecules such as glutamate and reactive oxygen species (ROS)/induced nitric oxide synthase (iNOS) [12] (Fig 2B) PubMed:25652642

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

a(CHEBI:"amyloid-beta polypeptide 42") increases bp(GO:"positive regulation of advanced glycation end-product receptor activity") View Subject | View Object

Excessive accumulation of Aβ1-42 stimulates microglial cells by signaling via receptor associated advanced glycation end products (RAGE) and peroxisome proliferator-activated receptor-γ (PPAR-γ), phosphorylates IKK proteins, and enhances NF-κB mediated transactivation of inflammatory cytokines and neurotoxic molecules such as glutamate and reactive oxygen species (ROS)/induced nitric oxide synthase (iNOS) [12] (Fig 2B) PubMed:25652642

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

a(CHEBI:"amyloid-beta polypeptide 42") increases bp(GO:"peroxisome proliferator activated receptor signaling pathway") View Subject | View Object

Excessive accumulation of Aβ1-42 stimulates microglial cells by signaling via receptor associated advanced glycation end products (RAGE) and peroxisome proliferator-activated receptor-γ (PPAR-γ), phosphorylates IKK proteins, and enhances NF-κB mediated transactivation of inflammatory cytokines and neurotoxic molecules such as glutamate and reactive oxygen species (ROS)/induced nitric oxide synthase (iNOS) [12] (Fig 2B) PubMed:25652642

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

a(CHEBI:"amyloid-beta polypeptide 42") increases p(MESH:"I-kappa B Proteins", pmod(Ph)) View Subject | View Object

Excessive accumulation of Aβ1-42 stimulates microglial cells by signaling via receptor associated advanced glycation end products (RAGE) and peroxisome proliferator-activated receptor-γ (PPAR-γ), phosphorylates IKK proteins, and enhances NF-κB mediated transactivation of inflammatory cytokines and neurotoxic molecules such as glutamate and reactive oxygen species (ROS)/induced nitric oxide synthase (iNOS) [12] (Fig 2B) PubMed:25652642

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

About

BEL Commons is developed and maintained in an academic capacity by Charles Tapley Hoyt and Daniel Domingo-Fernández at the Fraunhofer SCAI Department of Bioinformatics with support from the IMI project, AETIONOMY. It is built on top of PyBEL, an open source project. Please feel free to contact us here to give us feedback or report any issues. Also, see our Publishing Notes and Data Protection information.

If you find BEL Commons useful in your work, please consider citing: Hoyt, C. T., Domingo-Fernández, D., & Hofmann-Apitius, M. (2018). BEL Commons: an environment for exploration and analysis of networks encoded in Biological Expression Language. Database, 2018(3), 1–11.