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a(HBP:HBP00067)

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Entity

Name
HBP00067
Namespace
HBP
Namespace Version
20181221
Namespace URL
https://raw.githubusercontent.com/pharmacome/terminology/bd0996a28201cad363557315043c6392e31abf58/export/hbp.belns

Appears in Networks 2

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

In-Edges 19

a(CHEBI:"phorbol ester") association sec(a(HBP:HBP00067)) View Subject | View Object

Indeed, phorbol ester’s effect on sAPPalpha secretion and Abeta generation though activation of protein kinase C (PKC) has been known for a long time [201-203] PubMed:21214928

Appears in Networks:
Annotations
MeSH
Cell Membrane
Confidence
High
MeSH
Hippocampus
MeSH
Down Syndrome

a(CHEBI:estrogen) increases sec(a(HBP:HBP00067)) View Subject | View Object

Interestingly, the stimulation of sAPPalpha secretion by estrogen can be blocked by a PKC inhibitor, suggesting the involvement of a PKC-dependent pathway [200] PubMed:21214928

Appears in Networks:
Annotations
MeSH
Cell Membrane
Confidence
High
MeSH
Hippocampus
MeSH
Down Syndrome

bp(GO:"regulation of neuronal synaptic plasticity") association a(HBP:HBP00067) View Subject | View Object

In contrast to Abeta, sAPPalpha has an important role in neuronal plasticity/survival and is protective against excitotoxicity [42,43]. sAPPalpha also regulates neural stem cell proliferation and is important for early CNS development [57,58] PubMed:21214928

Appears in Networks:
Annotations
Confidence
High
MeSH
Temporal Lobe

complex(p(HGNC:APBA1), p(HGNC:APP)) association a(HBP:HBP00067) View Subject | View Object

APP interaction with mint proteins has been shown to affect APP processing by stabilizing cellular APP, altering both sAPPalpha and Abeta generation and secretion [166] PubMed:21214928

Appears in Networks:
Annotations
MeSH
Endosomes
Confidence
High
MeSH
Hippocampus
MeSH
Down Syndrome

complex(p(HGNC:APBA1), p(HGNC:APP)) association sec(a(HBP:HBP00067)) View Subject | View Object

APP interaction with mint proteins has been shown to affect APP processing by stabilizing cellular APP, altering both sAPPalpha and Abeta generation and secretion [166] PubMed:21214928

Appears in Networks:
Annotations
MeSH
Endosomes
Confidence
High
MeSH
Hippocampus
MeSH
Down Syndrome

complex(p(HGNC:APBA2), p(HGNC:APP)) association a(HBP:HBP00067) View Subject | View Object

APP interaction with mint proteins has been shown to affect APP processing by stabilizing cellular APP, altering both sAPPalpha and Abeta generation and secretion [166] PubMed:21214928

Appears in Networks:
Annotations
MeSH
Endosomes
Confidence
High
MeSH
Hippocampus
MeSH
Down Syndrome

complex(p(HGNC:APBA2), p(HGNC:APP)) association sec(a(HBP:HBP00067)) View Subject | View Object

APP interaction with mint proteins has been shown to affect APP processing by stabilizing cellular APP, altering both sAPPalpha and Abeta generation and secretion [166] PubMed:21214928

Appears in Networks:
Annotations
MeSH
Endosomes
Confidence
High
MeSH
Hippocampus
MeSH
Down Syndrome

complex(p(HGNC:APBA3), p(HGNC:APP)) association a(HBP:HBP00067) View Subject | View Object

APP interaction with mint proteins has been shown to affect APP processing by stabilizing cellular APP, altering both sAPPalpha and Abeta generation and secretion [166] PubMed:21214928

Appears in Networks:
Annotations
MeSH
Endosomes
Confidence
High
MeSH
Hippocampus
MeSH
Down Syndrome

complex(p(HGNC:APBA3), p(HGNC:APP)) association sec(a(HBP:HBP00067)) View Subject | View Object

APP interaction with mint proteins has been shown to affect APP processing by stabilizing cellular APP, altering both sAPPalpha and Abeta generation and secretion [166] PubMed:21214928

Appears in Networks:
Annotations
MeSH
Endosomes
Confidence
High
MeSH
Hippocampus
MeSH
Down Syndrome

complex(p(HGNC:APP), p(HGNC:LRP1B)) increases sec(a(HBP:HBP00067)) View Subject | View Object

An LRP-related protein 1B (LRP1B) has a similar effect, binding APP at the plasma membrane, preventing APP internalization, and leading to decreased Abeta generation and increased sAPPalpha secretion [189] PubMed:21214928

Appears in Networks:
Annotations
MeSH
Cell Membrane
Confidence
High
MeSH
Hippocampus
MeSH
Down Syndrome

composite(a(CHEBI:"phorbol ester"), p(HGNC:ADAM9), p(HGNC:APP)) increases a(HBP:HBP00067) View Subject | View Object

Co-expression of ADAM9 with APP promoted sAPPalpha production upon phorbol ester treatment, suggesting that ADAM9 possesses alpha-secretase activity [51] PubMed:21214928

Appears in Networks:
Annotations
Confidence
High
MeSH
Neurons

act(p(HGNC:PRKCA)) increases sec(a(HBP:HBP00067)) View Subject | View Object

Interestingly, the stimulation of sAPPalpha secretion by estrogen can be blocked by a PKC inhibitor, suggesting the involvement of a PKC-dependent pathway [200] PubMed:21214928

Appears in Networks:
Annotations
MeSH
Cell Membrane
Confidence
High
MeSH
Hippocampus
MeSH
Down Syndrome

p(HGNC:PRKCA) increases sec(a(HBP:HBP00067)) View Subject | View Object

PKC stimulates sAPPalpha secretion, reducing Abeta levels, even when the phosphorylation sites on APP are mutated or the entire cytoplasmic domain is deleted [204] PubMed:21214928

Appears in Networks:
Annotations
MeSH
Cell Membrane
Confidence
High
MeSH
Hippocampus
MeSH
Down Syndrome

path(MESH:"Alzheimer Disease") negativeCorrelation a(HBP:HBP00067) View Subject | View Object

A dramatically reduced ADAM10 protein level in the platelets of sporadic AD patients was also found to correlate with the significantly decreased sAPPalpha levels found in their platlets and cerebrospinal fluid [55] and the reduced alpha-secretase activity in the temporal cortex homogenates of AD patients [56] PubMed:21214928

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Blood Platelets
MeSH
Cerebrospinal Fluid

rxn(reactants(p(HGNC:APP)), products(a(HBP:HBP00067))) hasProduct a(HBP:HBP00067) View Subject | View Object

Appears in Networks:

p(HGNC:ADAM10) increases a(HBP:HBP00067) View Subject | View Object

Moderate neuronal over-expression of human ADAM10 increases sAPP-alpha production while reducing Abeta generation/ plaque formation in mice carrying the human APP V717I mutation, while expression of a catalytically-inactive form of the ADAM10 mutation increases the size and number of amyloid plaques in mouse brains (Postina et al. 2004) PubMed:22122372

Appears in Networks:
Annotations
Confidence
High
MeSH
Neurons

p(HGNC:ADAM17) increases a(HBP:HBP00067) View Subject | View Object

However, although sAPP-alpha generation is not affected in ADAM9/17 knock-down cell lines nor in mice carrying deficient ADAM9/17 genes (Weskamp et al. 2002; Kuhn et al. 2010), over-expression of ADAM9/17 does increase the level of sAPP-alpha under some conditions, suggesting that ADAM9 and ADAM17 are more likely involved in the regulated alpha-cleavage of APP rather than in constitutive alpha-cleavage PubMed:22122372

Appears in Networks:
Annotations
Confidence
High
MeSH
Neurons

p(HGNC:ADAM9) increases a(HBP:HBP00067) View Subject | View Object

However, although sAPP-alpha generation is not affected in ADAM9/17 knock-down cell lines nor in mice carrying deficient ADAM9/17 genes (Weskamp et al. 2002; Kuhn et al. 2010), over-expression of ADAM9/17 does increase the level of sAPP-alpha under some conditions, suggesting that ADAM9 and ADAM17 are more likely involved in the regulated alpha-cleavage of APP rather than in constitutive alpha-cleavage PubMed:22122372

Appears in Networks:
Annotations
Confidence
High
MeSH
Neurons

rxn(reactants(p(HGNC:APP)), products(a(HBP:HBP00067), a(HBP:HBP00072))) hasProduct a(HBP:HBP00067) View Subject | View Object

Appears in Networks:

Out-Edges 22

a(HBP:HBP00067) decreases bp(HBP:HBP00061) View Subject | View Object

While Abeta is neurotoxic, studies suggest that sAPPalpha is neuroprotective, making the subcellular distribution of APP an important factor in neurodegeneration [42-44] PubMed:21214928

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Neurons

a(HBP:HBP00067) negativeCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

A dramatically reduced ADAM10 protein level in the platelets of sporadic AD patients was also found to correlate with the significantly decreased sAPPalpha levels found in their platlets and cerebrospinal fluid [55] and the reduced alpha-secretase activity in the temporal cortex homogenates of AD patients [56] PubMed:21214928

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Blood Platelets
MeSH
Cerebrospinal Fluid

a(HBP:HBP00067) association bp(GO:"regulation of neuronal synaptic plasticity") View Subject | View Object

In contrast to Abeta, sAPPalpha has an important role in neuronal plasticity/survival and is protective against excitotoxicity [42,43]. sAPPalpha also regulates neural stem cell proliferation and is important for early CNS development [57,58] PubMed:21214928

Appears in Networks:
Annotations
Confidence
High
MeSH
Temporal Lobe

a(HBP:HBP00067) regulates bp(GO:"central nervous system formation") View Subject | View Object

In contrast to Abeta, sAPPalpha has an important role in neuronal plasticity/survival and is protective against excitotoxicity [42,43]. sAPPalpha also regulates neural stem cell proliferation and is important for early CNS development [57,58] PubMed:21214928

Appears in Networks:
Annotations
Confidence
High
MeSH
Temporal Lobe

a(HBP:HBP00067) decreases bp(HBP:HBP00068) View Subject | View Object

In contrast to Abeta, sAPPalpha has an important role in neuronal plasticity/survival and is protective against excitotoxicity [42,43]. sAPPalpha also regulates neural stem cell proliferation and is important for early CNS development [57,58] PubMed:21214928

Appears in Networks:
Annotations
Confidence
High
MeSH
Temporal Lobe

a(HBP:HBP00067) decreases bp(HBP:HBP00068) View Subject | View Object

We and others have also found that sAPPalpha can inhibit stress-induced CDK5 activation and participate in various neuroprotective reagent-mediated excitoprotection [44,59-61] PubMed:21214928

Appears in Networks:
Annotations
Confidence
High
MeSH
Neurons

a(HBP:HBP00067) regulates bp(GO:"stem cell proliferation") View Subject | View Object

In contrast to Abeta, sAPPalpha has an important role in neuronal plasticity/survival and is protective against excitotoxicity [42,43]. sAPPalpha also regulates neural stem cell proliferation and is important for early CNS development [57,58] PubMed:21214928

Appears in Networks:
Annotations
Confidence
High
MeSH
Neurons

a(HBP:HBP00067) decreases act(p(HGNC:CDK5)) View Subject | View Object

We and others have also found that sAPPalpha can inhibit stress-induced CDK5 activation and participate in various neuroprotective reagent-mediated excitoprotection [44,59-61] PubMed:21214928

Appears in Networks:
Annotations
Confidence
High
MeSH
Neurons

a(HBP:HBP00067) association complex(p(HGNC:APBA1), p(HGNC:APP)) View Subject | View Object

APP interaction with mint proteins has been shown to affect APP processing by stabilizing cellular APP, altering both sAPPalpha and Abeta generation and secretion [166] PubMed:21214928

Appears in Networks:
Annotations
MeSH
Endosomes
Confidence
High
MeSH
Hippocampus
MeSH
Down Syndrome

sec(a(HBP:HBP00067)) association complex(p(HGNC:APBA1), p(HGNC:APP)) View Subject | View Object

APP interaction with mint proteins has been shown to affect APP processing by stabilizing cellular APP, altering both sAPPalpha and Abeta generation and secretion [166] PubMed:21214928

Appears in Networks:
Annotations
MeSH
Endosomes
Confidence
High
MeSH
Hippocampus
MeSH
Down Syndrome

a(HBP:HBP00067) association complex(p(HGNC:APBA2), p(HGNC:APP)) View Subject | View Object

APP interaction with mint proteins has been shown to affect APP processing by stabilizing cellular APP, altering both sAPPalpha and Abeta generation and secretion [166] PubMed:21214928

Appears in Networks:
Annotations
MeSH
Endosomes
Confidence
High
MeSH
Hippocampus
MeSH
Down Syndrome

sec(a(HBP:HBP00067)) association complex(p(HGNC:APBA2), p(HGNC:APP)) View Subject | View Object

APP interaction with mint proteins has been shown to affect APP processing by stabilizing cellular APP, altering both sAPPalpha and Abeta generation and secretion [166] PubMed:21214928

Appears in Networks:
Annotations
MeSH
Endosomes
Confidence
High
MeSH
Hippocampus
MeSH
Down Syndrome

a(HBP:HBP00067) association complex(p(HGNC:APBA3), p(HGNC:APP)) View Subject | View Object

APP interaction with mint proteins has been shown to affect APP processing by stabilizing cellular APP, altering both sAPPalpha and Abeta generation and secretion [166] PubMed:21214928

Appears in Networks:
Annotations
MeSH
Endosomes
Confidence
High
MeSH
Hippocampus
MeSH
Down Syndrome

sec(a(HBP:HBP00067)) association complex(p(HGNC:APBA3), p(HGNC:APP)) View Subject | View Object

APP interaction with mint proteins has been shown to affect APP processing by stabilizing cellular APP, altering both sAPPalpha and Abeta generation and secretion [166] PubMed:21214928

Appears in Networks:
Annotations
MeSH
Endosomes
Confidence
High
MeSH
Hippocampus
MeSH
Down Syndrome

sec(a(HBP:HBP00067)) association a(CHEBI:"phorbol ester") View Subject | View Object

Indeed, phorbol ester’s effect on sAPPalpha secretion and Abeta generation though activation of protein kinase C (PKC) has been known for a long time [201-203] PubMed:21214928

Appears in Networks:
Annotations
MeSH
Cell Membrane
Confidence
High
MeSH
Hippocampus
MeSH
Down Syndrome

a(HBP:HBP00067) decreases bp(HBP:HBP00061) View Subject | View Object

APP can also be cleaved by alpha-secretase to form a soluble or secreted APP ectodomain (sAPP-alpha) that has been shown to be mostly neuro-protective PubMed:22122372

Appears in Networks:
Annotations
Confidence
High

sec(a(HBP:HBP00067)) decreases bp(HBP:HBP00061) View Subject | View Object

The constitutively secreted sAPP-alpha has been found to be neuro-protective (Mattson et al. 1993; Furukawa et al. 1996a,b; Han et al. 2005; Ma et al. 2009) PubMed:22122372

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Neurons

a(HBP:HBP00067) increases bp(GO:"cell adhesion") View Subject | View Object

sAPP-alpha is thought to promote neurite outgrowth and synaptogenesis as well as cell adhesion (Mattson 1997; Gakhar Koppole et al. 2008) PubMed:22122372

Appears in Networks:
Annotations
Confidence
High
MeSH
Neurons

a(HBP:HBP00067) increases bp(MESH:"Neuronal Outgrowth") View Subject | View Object

sAPP-alpha is thought to promote neurite outgrowth and synaptogenesis as well as cell adhesion (Mattson 1997; Gakhar Koppole et al. 2008) PubMed:22122372

Appears in Networks:
Annotations
Confidence
High
MeSH
Neurons

a(HBP:HBP00067) increases bp(GO:"synapse assembly") View Subject | View Object

sAPP-alpha is thought to promote neurite outgrowth and synaptogenesis as well as cell adhesion (Mattson 1997; Gakhar Koppole et al. 2008) PubMed:22122372

Appears in Networks:
Annotations
Confidence
High
MeSH
Neurons

a(HBP:HBP00067) increases bp(GO:learning) View Subject | View Object

In vivo studies have also shown that sAPP-alpha promotes learning and memory in animal models (Meziane et al. 1998; Taylor et al. 2008) PubMed:22122372

Appears in Networks:
Annotations
Confidence
High
MeSH
Neurons

a(HBP:HBP00067) increases bp(GO:memory) View Subject | View Object

In vivo studies have also shown that sAPP-alpha promotes learning and memory in animal models (Meziane et al. 1998; Taylor et al. 2008) PubMed:22122372

Appears in Networks:
Annotations
Confidence
High
MeSH
Neurons

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.