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p(HGNC:APOE)

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Entity

Name
APOE
Namespace
hgnc
Namespace Version
20180906
Namespace URL
https://raw.githubusercontent.com/pharmacome/terminology/b46b65c3da259b6e86026514dfececab7c22a11b/external/hgnc-names.belns

Appears in Networks 6

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

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

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

Tau Modifications v1.9.5

Tau Modifications Sections of NESTOR

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

Activity-dependent neuroprotective protein deficiency models synaptic and developmental phenotypes of autism-like syndrome v1.0.0

In-Edges 16

bp(GO:"lipid metabolic process") association p(HGNC:APOE) View Subject | View Object

The apolipoprotein E type 4 allele (APOE-epsilon4) encodes the APOE lipoprotein, which through its lipid transport function plays a role in lipid metabolism. APOE-epsilon4 has been found to be a major risk factor for late familial or sporadic AD, with a strong gene-dosage effect such that the number of APOE-epsilon4 alleles correlated positively with the risk of developing AD and the age of onset (Corder et al., 1993). PubMed:19293145

Appears in Networks:

p(HGNCGENEFAMILY:"Cholinergic receptors nicotinic subunits") association p(HGNC:APOE) View Subject | View Object

There is evidence that ApoE directly interacts with nAChRs. An APOE-derived peptide blocks nAChRs on rat hippocampal slices with a submicromolar affinity, and this action is dependent on an arginine-rich segment of the APOE peptide (Klein and Yakel, 2004). Block of heterologously expressed alpha7 nAChRs is greater than that for alpha4beta2 or alpha2beta2 nAChRs (Gay et al., 2006). This block of alpha7 receptors is abolished when alpha7 Trp55 is mutated to alanine, providing strong evidence that it results from a direct interaction between the peptide and the receptors (Gay et al., 2007), and the effects of other substitutions of Trp55 suggests that this interaction is hydrophobic PubMed:19293145

Appears in Networks:

complex(p(HGNC:APOE), p(HGNC:CHRNA7)) hasComponent p(HGNC:APOE) View Subject | View Object

Appears in Networks:

g(HGNC:APOE) increases p(HGNC:APOE) View Subject | View Object

The apolipoprotein E type 4 allele (APOE-epsilon4) encodes the APOE lipoprotein, which through its lipid transport function plays a role in lipid metabolism. APOE-epsilon4 has been found to be a major risk factor for late familial or sporadic AD, with a strong gene-dosage effect such that the number of APOE-epsilon4 alleles correlated positively with the risk of developing AD and the age of onset (Corder et al., 1993). PubMed:19293145

Appears in Networks:

a(CHEBI:"GW 3965") increases p(HGNC:APOE) View Subject | View Object

Importantly, this study utilized the LXR agonist, GW3965, to activate the LXRs and induce the expression of both ApoE and ABCA1. PubMed:21718217

Appears in Networks:
Annotations
Confidence
High

a(CHEBI:Honokiol) increases p(HGNC:APOE) View Subject | View Object

More recently, a naturally occurring RXR agonist, honokiol, has been identified. This agonist is capable of activating RXR/LXR heterodimers and has been shown to induce the expression of ABCA1 and ApoE and should be tested in AD models [75,78]. PubMed:21718217

Appears in Networks:
Annotations
Confidence
High

a(CHEBI:bexarotene) increases p(HGNC:APOE) View Subject | View Object

Bexarotene is a highly specific RXR agonist and is currently FDA approved with a favorable side effect profile. Studies in our laboratory have shown that treatment of APP/ PS1 animals with bexarotene for only 3 days results in a dramatic induction of ApoE and ABCA1 and the rapid reversal of AD-associated pathological hallmarks including reduction in amyloid deposition and deficits in behavior as well as neural networks. PubMed:21718217

Appears in Networks:
Annotations
Confidence
High

act(p(FPLX:RXR)) increases p(HGNC:APOE) View Subject | View Object

RXR activation by numerous ligands has shown to increase levels of both ApoE and ABCA1 in vitro [74-76]. PubMed:21718217

Appears in Networks:
Annotations
Confidence
High

p(HGNC:NR1H3) increases p(HGNC:APOE) View Subject | View Object

Numerous studies have shown that both PPAR-g and LXRs induce the expression of ApoE and ABCA1 and it is through the expression of these proteins that they exert their effects on amyloid pathology. PubMed:21718217

Appears in Networks:
Annotations
Confidence
High
MeSH
Microglia

act(p(HGNC:NR1H3)) increases act(p(HGNC:APOE)) View Subject | View Object

LXR activation increased the ApoE particle size of all human ApoE isoforms, suggesting that activation of this pathways may enhance Ab clearance regardless of the ApoE allele expressed [13]. PubMed:21718217

Appears in Networks:
Annotations
Confidence
Medium

p(HGNC:ABCA1) increases p(HGNC:APOE) View Subject | View Object

The loss of abca1 resulted in not only the reduction of ApoE levels but also a paradoxical increase in Ab deposition in the brain parenchyma of these animals owing to enhanced deposition of poorly lipidated ApoE in the brain [50-52]. PubMed:21718217

Appears in Networks:
Annotations
Confidence
High

p(HGNC:PPARG) increases p(HGNC:APOE) View Subject | View Object

Numerous studies have shown that both PPAR-g and LXRs induce the expression of ApoE and ABCA1 and it is through the expression of these proteins that they exert their effects on amyloid pathology. PubMed:21718217

Appears in Networks:
Annotations
Confidence
High
MeSH
Microglia

a(CHEBI:"amyloid-beta") increases act(p(HGNC:APOE)) View Subject | View Object

Aβ has been shown to upregulate APOE in astroglial cells. This upregulation was inhibited by decoy-κB nucleotides supporting a critical role for NFκB in APOE function PubMed:25652642

Appears in Networks:
Annotations
MeSH
Astrocytes
MeSH
Alzheimer Disease

complex(GO:"NF-kappaB complex") association act(p(HGNC:APOE)) View Subject | View Object

Aβ has been shown to upregulate APOE in astroglial cells. This upregulation was inhibited by decoy-κB nucleotides supporting a critical role for NFκB in APOE function PubMed:25652642

Appears in Networks:
Annotations
MeSH
Astrocytes
MeSH
Alzheimer Disease

a(PUBCHEM:9832404) association p(HGNC:APOE) View Subject | View Object

In the 3-month-old hippocampi (Figure 4B), we found significant sex-dependent changes for Adnp+/– gene regulation and NAP rescue in the following genes in male mice: (a) apolipoprotein E (Apoe), the lead gene for Alzheimer’s disease risk, which was shown before to be a major gene regulated by ADNP (10, 13); (b) Gm21949, which is suggested to play a role in calcium-mediated responses, action potential conduction in myelinated cells, and axonal outgrowth and guidance (6); (c) lipase A (Lipa), which is related to lipid metabolism and was previously shown to be regulated by the Adnp genotype in mice (3); (d) autism-associated neuroligin 2 (Nlgn2), a postsynaptic membrane cell adhesion protein that mediates the formation and maintenance of synapses between neurons (12); (e) paired box protein 6 (Pax6), a key regulator in glutamatergic neuronal differentiation (38) and cortical development (39), which was shown before by us to be regulated by ADNP (complete knockout of Adnp rendered Pax6 expression undetectable in the brain primordium, contrasting with increased expression in Adnp+/– embryos [ref. 1] and in subcortical brain domains of 2-month-old male Adnp+/– mice [ref. 3]); and (f) Wolframin endoplasmic reticulum transmembrane glycoprotein (Wfs1), which is associated with neurodegeneration and cellular calcium homeostasis regulation and was previously shown to be regulated by NAP (34). PubMed:30106381

Appears in Networks:
Annotations
MeSH
Hippocampus
Gender
Male

p(HGNC:ADNP) regulates p(HGNC:APOE) View Subject | View Object

In the 3-month-old hippocampi (Figure 4B), we found significant sex-dependent changes for Adnp+/– gene regulation and NAP rescue in the following genes in male mice: (a) apolipoprotein E (Apoe), the lead gene for Alzheimer’s disease risk, which was shown before to be a major gene regulated by ADNP (10, 13); (b) Gm21949, which is suggested to play a role in calcium-mediated responses, action potential conduction in myelinated cells, and axonal outgrowth and guidance (6); (c) lipase A (Lipa), which is related to lipid metabolism and was previously shown to be regulated by the Adnp genotype in mice (3); (d) autism-associated neuroligin 2 (Nlgn2), a postsynaptic membrane cell adhesion protein that mediates the formation and maintenance of synapses between neurons (12); (e) paired box protein 6 (Pax6), a key regulator in glutamatergic neuronal differentiation (38) and cortical development (39), which was shown before by us to be regulated by ADNP (complete knockout of Adnp rendered Pax6 expression undetectable in the brain primordium, contrasting with increased expression in Adnp+/– embryos [ref. 1] and in subcortical brain domains of 2-month-old male Adnp+/– mice [ref. 3]); and (f) Wolframin endoplasmic reticulum transmembrane glycoprotein (Wfs1), which is associated with neurodegeneration and cellular calcium homeostasis regulation and was previously shown to be regulated by NAP (34). PubMed:30106381

Appears in Networks:
Annotations
MeSH
Hippocampus
Gender
Male

Out-Edges 12

p(HGNC:APOE) association bp(GO:"lipid metabolic process") View Subject | View Object

The apolipoprotein E type 4 allele (APOE-epsilon4) encodes the APOE lipoprotein, which through its lipid transport function plays a role in lipid metabolism. APOE-epsilon4 has been found to be a major risk factor for late familial or sporadic AD, with a strong gene-dosage effect such that the number of APOE-epsilon4 alleles correlated positively with the risk of developing AD and the age of onset (Corder et al., 1993). PubMed:19293145

Appears in Networks:

p(HGNC:APOE) association p(HGNCGENEFAMILY:"Cholinergic receptors nicotinic subunits") View Subject | View Object

There is evidence that ApoE directly interacts with nAChRs. An APOE-derived peptide blocks nAChRs on rat hippocampal slices with a submicromolar affinity, and this action is dependent on an arginine-rich segment of the APOE peptide (Klein and Yakel, 2004). Block of heterologously expressed alpha7 nAChRs is greater than that for alpha4beta2 or alpha2beta2 nAChRs (Gay et al., 2006). This block of alpha7 receptors is abolished when alpha7 Trp55 is mutated to alanine, providing strong evidence that it results from a direct interaction between the peptide and the receptors (Gay et al., 2007), and the effects of other substitutions of Trp55 suggests that this interaction is hydrophobic PubMed:19293145

Appears in Networks:

p(HGNC:APOE) increases a(CHEBI:"high-density lipoprotein") View Subject | View Object

ApoE acts to scaffold the formation of high-density lipoproteins (HDL) that function to transport cholesterol and lipids throughout the body and in the brain. PubMed:21718217

Appears in Networks:
Annotations
Confidence
High
MeSH
Microglia

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

They were able to show that the lipidation of ApoE enhanced the degradation of soluble species of Ab by neprilysin in the endolytic compartments of microglia as well as extracellularly through the actions of the insulindegrading enzyme (IDE) [13]. PubMed:21718217

Appears in Networks:
Annotations
Confidence
High
MeSH
Microglia

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

LXR activation increased the ApoE particle size of all human ApoE isoforms, suggesting that activation of this pathways may enhance Ab clearance regardless of the ApoE allele expressed [13]. PubMed:21718217

Appears in Networks:
Annotations
Confidence
Medium

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

which is located on the abluminal side of the brain endo- thelium,140 does not directly bind and extrude Aβ,141 but mediates Aβ clearance in an ApoE-dependent manner. PubMed:26195256

Appears in Networks:
Annotations
MeSH
Hippocampus
MeSH
Temporal Lobe

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

ApoE is a cholesterol transporter that competes with Aβ for efflux by LRP1 from the interstitium into the circula- tion; PubMed:26195256

Appears in Networks:
Annotations
MeSH
Hippocampus
MeSH
Temporal Lobe

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

competition for shared receptors is the primary mechanism by which ApoE mediates Aβ clearance PubMed:26195256

Appears in Networks:
Annotations
MeSH
Hippocampus
MeSH
Temporal Lobe

p(HGNC:APOE) hasVariant p(HGNC:APOE, pmod(Ub)) View Subject | View Object

Appears in Networks:

act(p(HGNC:APOE)) association complex(GO:"NF-kappaB complex") View Subject | View Object

Aβ has been shown to upregulate APOE in astroglial cells. This upregulation was inhibited by decoy-κB nucleotides supporting a critical role for NFκB in APOE function PubMed:25652642

Appears in Networks:
Annotations
MeSH
Astrocytes
MeSH
Alzheimer Disease

p(HGNC:APOE) association a(PUBCHEM:9832404) View Subject | View Object

In the 3-month-old hippocampi (Figure 4B), we found significant sex-dependent changes for Adnp+/– gene regulation and NAP rescue in the following genes in male mice: (a) apolipoprotein E (Apoe), the lead gene for Alzheimer’s disease risk, which was shown before to be a major gene regulated by ADNP (10, 13); (b) Gm21949, which is suggested to play a role in calcium-mediated responses, action potential conduction in myelinated cells, and axonal outgrowth and guidance (6); (c) lipase A (Lipa), which is related to lipid metabolism and was previously shown to be regulated by the Adnp genotype in mice (3); (d) autism-associated neuroligin 2 (Nlgn2), a postsynaptic membrane cell adhesion protein that mediates the formation and maintenance of synapses between neurons (12); (e) paired box protein 6 (Pax6), a key regulator in glutamatergic neuronal differentiation (38) and cortical development (39), which was shown before by us to be regulated by ADNP (complete knockout of Adnp rendered Pax6 expression undetectable in the brain primordium, contrasting with increased expression in Adnp+/– embryos [ref. 1] and in subcortical brain domains of 2-month-old male Adnp+/– mice [ref. 3]); and (f) Wolframin endoplasmic reticulum transmembrane glycoprotein (Wfs1), which is associated with neurodegeneration and cellular calcium homeostasis regulation and was previously shown to be regulated by NAP (34). PubMed:30106381

Appears in Networks:
Annotations
MeSH
Hippocampus
Gender
Male

p(HGNC:APOE) increases path(MESH:"Alzheimer Disease") View Subject | View Object

In the 3-month-old hippocampi (Figure 4B), we found significant sex-dependent changes for Adnp+/– gene regulation and NAP rescue in the following genes in male mice: (a) apolipoprotein E (Apoe), the lead gene for Alzheimer’s disease risk, which was shown before to be a major gene regulated by ADNP (10, 13); (b) Gm21949, which is suggested to play a role in calcium-mediated responses, action potential conduction in myelinated cells, and axonal outgrowth and guidance (6); (c) lipase A (Lipa), which is related to lipid metabolism and was previously shown to be regulated by the Adnp genotype in mice (3); (d) autism-associated neuroligin 2 (Nlgn2), a postsynaptic membrane cell adhesion protein that mediates the formation and maintenance of synapses between neurons (12); (e) paired box protein 6 (Pax6), a key regulator in glutamatergic neuronal differentiation (38) and cortical development (39), which was shown before by us to be regulated by ADNP (complete knockout of Adnp rendered Pax6 expression undetectable in the brain primordium, contrasting with increased expression in Adnp+/– embryos [ref. 1] and in subcortical brain domains of 2-month-old male Adnp+/– mice [ref. 3]); and (f) Wolframin endoplasmic reticulum transmembrane glycoprotein (Wfs1), which is associated with neurodegeneration and cellular calcium homeostasis regulation and was previously shown to be regulated by NAP (34). PubMed:30106381

Appears in Networks:
Annotations
MeSH
Hippocampus
Gender
Male

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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.