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p(HGNC:APP, frag("672_713"))

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Entity

Name
APP
Namespace
HGNC
Namespace Version
20180215
Namespace URL
https://arty.scai.fraunhofer.de/artifactory/bel/namespace/hgnc/hgnc-20180215.belns

Appears in Networks 3

APP processing in Alzheimer's disease v1.0.1

APP processing in Alzheimer's disease

Proteolytic processing of Alzeimer's beta-amyloid precursor protein v1.0.1

Tau Modifications v1.9.5

Tau Modifications Sections of NESTOR

In-Edges 11

p(HGNC:APP) hasVariant p(HGNC:APP, frag("672_713")) View Subject | View Object

Appears in Networks:

p(HGNC:BACE1) increases p(HGNC:APP, frag("672_713")) View Subject | View Object

BACE1 deficiency in AD model mice have been shown to rescue cholinergic dysfunction, neuronal loss and memory deficits, correlating with a dramatic reduction in Abeta40/42 levels [79-81] PubMed:21214928

Appears in Networks:
Annotations
MeSH
Endosomes
Confidence
Medium
MeSH
Neurons

a(HBP:HBP00069) increases p(HGNC:APP, frag("672_713")) View Subject | View Object

C31 also appears to induce a caspase-independent toxicity by selectively increasing Abeta42 (Dumanchin-Njock et al. 2001) PubMed:22122372

Appears in Networks:
Annotations
Confidence
High
MeSH
Neurons

p(HGNC:PSEN1, var("?")) increases p(HGNC:APP, frag("672_713")) View Subject | View Object

Transgenic mice over-expressing PSs with FAD mutations show significantly increased Abeta42 levels, suggesting that PS mutations probably induce AD by producing more of the hydrophobic Abeta42 form (Duff et al. 1996; Qian et al. 1998) PubMed:22122372

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Neurons

p(HGNC:PSEN2, var("?")) increases p(HGNC:APP, frag("672_713")) View Subject | View Object

Transgenic mice over-expressing PSs with FAD mutations show significantly increased Abeta42 levels, suggesting that PS mutations probably induce AD by producing more of the hydrophobic Abeta42 form (Duff et al. 1996; Qian et al. 1998) PubMed:22122372

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Neurons

a(CHEBI:glyceraldehyde) decreases p(HGNC:APP, frag("672_713")) View Subject | View Object

Aβ 42 in the medium decreased in a GA dose-dependent manner (Fig. 3a). In contrast, GA significantly increased tau and its phosphorylated form, p-tauT181 (Fig. 3b,c) in the medium. In addition, VEGF (Fig. 3e) and TGF-β (Fig. 3f), which are also AD biomarkers, were increased when the concentration of GA added was greater than 0.7 mM. PubMed:26304819

Appears in Networks:

p(HGNC:APP, pmod(Ph, Thr, 668)) regulates sec(p(HGNC:APP, frag("672_713"))) View Subject | View Object

Furthermore, DAPK1-induced APP phosphorylation was suppressed when DAPK1 ΔDD was introduced (Fig. 4G), indicating that DAPK1 regulates Aβ secretion through APP Thr668 phosphorylation. PubMed:27094130

Appears in Networks:

p(HGNC:DAPK1) increases sec(p(HGNC:APP, frag("672_713"))) View Subject | View Object

DAPK1, but not its kinase deficient mutant (K42A), significantly increased human Aβ secretion in neuronal cell culture models. Moreover, knockdown of DAPK1 expression or inhibition of DAPK1 catalytic activity significantly decreased Aβ secretion. Furthermore, DAPK1, but not K42A, triggered Thr668 phosphorylation of APP, which may initiate and facilitate amyloidogenic APP processing leading to the generation of Aβ. PubMed:27094130

Appears in Networks:

act(p(HGNC:DAPK1), ma(kin)) positiveCorrelation sec(p(HGNC:APP, frag("672_713"))) View Subject | View Object

DAPK1, but not its kinase deficient mutant (K42A), significantly increased human Aβ secretion in neuronal cell culture models. Moreover, knockdown of DAPK1 expression or inhibition of DAPK1 catalytic activity significantly decreased Aβ secretion. Furthermore, DAPK1, but not K42A, triggered Thr668 phosphorylation of APP, which may initiate and facilitate amyloidogenic APP processing leading to the generation of Aβ. PubMed:27094130

Appears in Networks:

p(HGNC:SUMO3) increases p(HGNC:APP, frag("672_713")) View Subject | View Object

SUMO3 overexpression significantly increased Abeta40 and Abeta42 secretion, which was accompanied by an increase in full-length APP and its C-terminal fragments. These effects of SUMO3 were independent of its covalent attachment or chain formation, as mutants lacking the motifs responsible for SUMO chain formation or SUMO conjugation led to similar changes in Abeta. SUMO3 overexpression also up-regulated the expression of the transmembrane protease BACE (beta-amyloid-cleaving enzyme), but failed to affect levels of several other unrelated proteins. PubMed:17346237

Appears in Networks:

p(MGI:Sirt3) negativeCorrelation p(HGNC:APP, frag("672_713")) View Subject | View Object

After pretreating hTau neurons with oligo Aβ-42 (1000 ng/ml), Sirt3 levels were reduced (Fig. 6b and e). This reduction in Sirt3 was translated into an increase in total tau and Ac-tau. PubMed:29540553

Appears in Networks:

Out-Edges 13

p(HGNC:APP, frag("672_713")) increases a(HBP:HBP00038) View Subject | View Object

There are two main toxic species, Ab40 and Ab42, with Abeta42 more hydrophobic and more prone to fibril formation while only making up about 10% of the Abeta peptide produced [143] PubMed:21214928

Appears in Networks:
Annotations
MeSH
Endosomes
Confidence
Medium
MeSH
Neurons

p(HGNC:APP, frag("672_713")) increases a(HBP:HBP00038) View Subject | View Object

Studies done on familial AD (FAD) mutations consistently show increases in the ratio of Abeta42/40 [105,144], suggesting that elevated levels of Abeta42 relative to Abeta40 is critical for AD pathogenesis, probably by providing the core for Abeta assembly into oligomers, fibrils and amyloidogenic plaques [145,146] PubMed:21214928

Appears in Networks:
Annotations
MeSH
Endosomes
Confidence
High
MeSH
Neurons

p(HGNC:APP, frag("672_713")) increases path(MESH:"Alzheimer Disease") View Subject | View Object

Studies done on familial AD (FAD) mutations consistently show increases in the ratio of Abeta42/40 [105,144], suggesting that elevated levels of Abeta42 relative to Abeta40 is critical for AD pathogenesis, probably by providing the core for Abeta assembly into oligomers, fibrils and amyloidogenic plaques [145,146] PubMed:21214928

Appears in Networks:
Annotations
MeSH
Endosomes
Confidence
High
MeSH
Neurons

p(HGNC:APP, frag("672_713")) increases a(HBP:HBP00022) View Subject | View Object

Studies done on familial AD (FAD) mutations consistently show increases in the ratio of Abeta42/40 [105,144], suggesting that elevated levels of Abeta42 relative to Abeta40 is critical for AD pathogenesis, probably by providing the core for Abeta assembly into oligomers, fibrils and amyloidogenic plaques [145,146] PubMed:21214928

Appears in Networks:
Annotations
MeSH
Endosomes
Confidence
High
MeSH
Neurons

p(HGNC:APP, frag("672_713")) increases path(MESH:"Plaque, Amyloid") View Subject | View Object

Studies done on familial AD (FAD) mutations consistently show increases in the ratio of Abeta42/40 [105,144], suggesting that elevated levels of Abeta42 relative to Abeta40 is critical for AD pathogenesis, probably by providing the core for Abeta assembly into oligomers, fibrils and amyloidogenic plaques [145,146] PubMed:21214928

Appears in Networks:
Annotations
MeSH
Endosomes
Confidence
High
MeSH
Neurons

p(HGNC:APP, frag("672_713")) increases path(MESH:"Plaque, Amyloid") View Subject | View Object

Among the various Ab peptides generated by the multiplesite cleavages of secretases, Abeta 42 has proved to be more hydrophobic and amyloidogenic than others (Burdick et al. 1992) PubMed:22122372

Appears in Networks:
Annotations
Confidence
High
MeSH
Neurons

p(HGNC:APP, frag("672_713")) increases path(MESH:"Plaque, Amyloid") View Subject | View Object

Studies also suggest that increased Abeta 42 levels probably provide the core for oligomerization, fibrillation and amyloid plaque generation (Jarrett et al. 1993; Iwatsubo et al. 1994) PubMed:22122372

Appears in Networks:
Annotations
Confidence
High
MeSH
Neurons

p(HGNC:APP, frag("672_713")) increases a(HBP:HBP00022) View Subject | View Object

Studies also suggest that increased Abeta 42 levels probably provide the core for oligomerization, fibrillation and amyloid plaque generation (Jarrett et al. 1993; Iwatsubo et al. 1994) PubMed:22122372

Appears in Networks:
Annotations
Confidence
High
MeSH
Neurons

p(HGNC:APP, frag("672_713")) increases a(HBP:HBP00038) View Subject | View Object

Studies also suggest that increased Abeta 42 levels probably provide the core for oligomerization, fibrillation and amyloid plaque generation (Jarrett et al. 1993; Iwatsubo et al. 1994) PubMed:22122372

Appears in Networks:
Annotations
Confidence
High
MeSH
Neurons

sec(p(HGNC:APP, frag("672_713"))) positiveCorrelation act(p(HGNC:DAPK1), ma(kin)) View Subject | View Object

DAPK1, but not its kinase deficient mutant (K42A), significantly increased human Aβ secretion in neuronal cell culture models. Moreover, knockdown of DAPK1 expression or inhibition of DAPK1 catalytic activity significantly decreased Aβ secretion. Furthermore, DAPK1, but not K42A, triggered Thr668 phosphorylation of APP, which may initiate and facilitate amyloidogenic APP processing leading to the generation of Aβ. PubMed:27094130

Appears in Networks:

p(HGNC:APP, frag("672_713")) negativeCorrelation p(MGI:Sirt3) View Subject | View Object

After pretreating hTau neurons with oligo Aβ-42 (1000 ng/ml), Sirt3 levels were reduced (Fig. 6b and e). This reduction in Sirt3 was translated into an increase in total tau and Ac-tau. PubMed:29540553

Appears in Networks:

p(HGNC:APP, frag("672_713")) increases p(MGI:Mapt, pmod(Ac)) View Subject | View Object

We found that NO production and tau acetylation at Lys280 occurred in the brain tissue in mice and in cultured mouse cortical neurons in response to exposure to amyloid-β1-42 (Aβ1-42), a peptide that is also implicated in AD. An increased abundance of NO facilitated the S-nitrosylation (SNO) of glyceraldehyde-3-phosphate dehydrogenase (GAPDH). S-nitrosylated GAPDH (GAPDH-SNO) promoted the acetylation and activation of the acetyltransferase p300 and facilitated the nitrosylation and inactivation of the deacetylase sirtuin 1 (SIRT1). The abundance of GAPDH-SNO was increased in postmortem brain samples from AD patients. Preventing the increase in GAPDH-SNO abundance in both cultured neurons and mice, either by overexpression of the nitrosylation mutant of GAPDH (GAPDH C150S) or by treatment with the GAPDH nitrosylation inhibitor CGP3466B (also known as omigapil), abrogated Aβ1-42-induced tau acetylation, memory impairment, and locomotor dysfunction in mice, suggesting that this drug might be repurposed to treat patients with AD. PubMed:29559585

Appears in Networks:

p(HGNC:APP, frag("672_713")) increases a(CHEBI:"nitric oxide") View Subject | View Object

We found that NO production and tau acetylation at Lys280 occurred in the brain tissue in mice and in cultured mouse cortical neurons in response to exposure to amyloid-β1-42 (Aβ1-42), a peptide that is also implicated in AD. An increased abundance of NO facilitated the S-nitrosylation (SNO) of glyceraldehyde-3-phosphate dehydrogenase (GAPDH). S-nitrosylated GAPDH (GAPDH-SNO) promoted the acetylation and activation of the acetyltransferase p300 and facilitated the nitrosylation and inactivation of the deacetylase sirtuin 1 (SIRT1). The abundance of GAPDH-SNO was increased in postmortem brain samples from AD patients. Preventing the increase in GAPDH-SNO abundance in both cultured neurons and mice, either by overexpression of the nitrosylation mutant of GAPDH (GAPDH C150S) or by treatment with the GAPDH nitrosylation inhibitor CGP3466B (also known as omigapil), abrogated Aβ1-42-induced tau acetylation, memory impairment, and locomotor dysfunction in mice, suggesting that this drug might be repurposed to treat patients with AD. PubMed:29559585

Appears in Networks:

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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.