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p(HGNC:BACE1)

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Entity

Name
BACE1
Namespace
hgnc
Namespace Version
20180906
Namespace URL
https://raw.githubusercontent.com/pharmacome/terminology/b46b65c3da259b6e86026514dfececab7c22a11b/external/hgnc-names.belns

Appears in Networks 25

Identification of a novel aspartic protease (Asp 2) as beta-secretase v1.0.0

Amyloid Precursor Protein Trafficking, Processing, and Function v1.0.0

Amyloid Precursor Protein Trafficking, Processing, and Function by Thinakaran, et al., 2008

Effects of peptides derived from BACE1 catalytic domain on APP processing v1.0.0

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

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

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

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

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

Tau Modifications v1.9.5

Tau Modifications Sections of NESTOR

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

Alzheimer’s disease and the autophagic-lysosomal system v1.0.0

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

Alzheimer's disease pathological lesions activate the spleen tyrosine kinase. v1.0.0

New insights into the role of microRNAs and long noncoding RNAs in most common neurodegenerative diseases v1.0.0

Increased NF-κB signalling up-regulates BACE1 expression and its therapeutic potential in Alzheimer's disease. v1.0.0

Nuclear Factor Kappa-light-chain-enhancer of Activated B Cells (NF-κB) - a Friend, a Foe, or a Bystander - in the Neurodegenerative Cascade and Pathogenesis of Alzheimer's Disease 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 65

a(HBP:APP695) association p(HGNC:BACE1) View Subject | View Object

Using the same anti-peptide sera we can detect expression of endogenous Asp 2 in SH-SY5Y cells stably expressing the 695 isoform of APP (SH-SY5Y APP-695) and in COS-7 cells expressing the 751 isoform of APP (COS-7 APP-751). The level of Asp 2 is increased upon transient transfection with the protein. PubMed:10656250

Appears in Networks:
Annotations
Experimental Factor Ontology (EFO)
SH-SY5Y

a(HBP:APP751) association p(HGNC:BACE1) View Subject | View Object

Using the same anti-peptide sera we can detect expression of endogenous Asp 2 in SH-SY5Y cells stably expressing the 695 isoform of APP (SH-SY5Y APP-695) and in COS-7 cells expressing the 751 isoform of APP (COS-7 APP-751). The level of Asp 2 is increased upon transient transfection with the protein. PubMed:10656250

Appears in Networks:
Annotations
Experimental Factor Ontology (EFO)
COS-7 cell

p(HGNC:APP, loc(GO:"endoplasmic reticulum")) association p(HGNC:BACE1, loc(GO:"endoplasmic reticulum")) View Subject | View Object

APP clearly localizes to the Golgi/endoplasmic reticulum region as revealed by distinctive juxtanuclear staining and a more generalized reticular staining throughout the cell (Figs. 6b and 6g). Asp 2 shows essentially the same subcellular distribution as revealed by simultaneous detection of myc-tagged Asp 2 and APP in COS-7 APP-751 cells (compare Figs. 6f and 6g), and merging of the confocal images for APP and Asp 2 indicates colocalization (Fig. 6h). PubMed:10656250

Appears in Networks:

path(MESH:"Alzheimer Disease") increases p(HGNC:BACE1) View Subject | View Object

We have examined the distribution of Asp 2 in AD hippocampus using a polyclonal antiserum raised to a peptide sequence derived from Asp 2 (see Experimental Methods).We see clear neuronal staining but there is no staining associated with astrocytes, microglia, or oligodendrocytes (Figs. 5a and 5b). PubMed:10656250

Appears in Networks:
Annotations
MeSH
Hippocampus

p(HGNC:BACE1, frag("228_236")) causesNoChange act(p(HGNC:BACE1)) View Subject | View Object

These results suggest that BACE1 derived peptides do not directly inhibit BACE activities in vitro when the fluorogenic peptides are used as a substrate. PubMed:17293005

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p(HGNC:BACE1, frag("67_78")) causesNoChange act(p(HGNC:BACE1)) View Subject | View Object

These results suggest that BACE1 derived peptides do not directly inhibit BACE activities in vitro when the fluorogenic peptides are used as a substrate. PubMed:17293005

Appears in Networks:

a(CHEBI:testosterone) decreases p(HGNC:BACE1) View Subject | View Object

However, a recent study blocking the conversion of testosterone to estrogen found an estrogen-independent improvement in cognitive function and lowering of plaque formation along with a decrease in BACE1 mRNA, protein level, and activity [211]. In addition, testosterone may also reduce the protein level of PS1 [196] PubMed:21214928

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

a(CHEBI:testosterone) decreases act(p(HGNC:BACE1)) View Subject | View Object

However, a recent study blocking the conversion of testosterone to estrogen found an estrogen-independent improvement in cognitive function and lowering of plaque formation along with a decrease in BACE1 mRNA, protein level, and activity [211]. In addition, testosterone may also reduce the protein level of PS1 [196] PubMed:21214928

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

act(a(HBP:HBP00071), ma(tscript)) regulates p(HGNC:BACE1) View Subject | View Object

In a similar fashion, released AICD has been shown to possess transactivation activity and can regulate transcription of multiple genes including APP, GSK- 3b, KAI1, neprilysin, BACE1, p53, EGFR, and LRP1 [127-132] PubMed:21214928

Appears in Networks:
Annotations
MeSH
Endosomes
Confidence
Medium
MeSH
Neurons

complex(p(HGNC:APP), p(HGNC:KIF5B)) regulates act(p(HGNC:BACE1)) View Subject | View Object

During its transport, APP was found to interact with kinesin-I and functions as a kinesin-I membrane receptor to mediate axonal transport of beta-secretase (BACE1) and PS1 [26,27] PubMed:21214928

Appears in Networks:
Annotations
Confidence
High
MeSH
Neurons

complex(p(HGNC:BACE1), p(HGNC:GGA1)) hasComponent p(HGNC:BACE1) View Subject | View Object

Appears in Networks:

complex(p(HGNC:BACE1), p(HGNC:RTN4)) hasComponent p(HGNC:BACE1) View Subject | View Object

Appears in Networks:

composite(p(HBP:"gamma-secretase"), p(HGNC:APP), p(HGNC:BACE1)) hasComponent p(HGNC:BACE1) View Subject | View Object

Appears in Networks:

bp(GO:"MAPK cascade") increases p(HGNC:BACE1) View Subject | View Object

When APP/PS1/tau triple transgenic (3×Tg) AD mice are treated with the selective M1 mAChR agonist AF267B, the endogenous level of BACE1 decreases via an unclear mechanism, accompanied by a decreased Abeta level[77]. However, another study found that stimulation of M1 mAChR upregulates BACE1 levels in SK-SH-SY5Y cells via the PKC and MAPK signaling cascades[78]. We recently found that M1 mAChR directly interacts with BACE1 and mediates its proteasomal degradation[79]. These results suggest that M1 mAChR modulates BACE1 in a mixed manner. PubMed:24590577

Appears in Networks:

act(p(HGNC:CHRM1)) increases p(HGNC:BACE1) View Subject | View Object

When APP/PS1/tau triple transgenic (3×Tg) AD mice are treated with the selective M1 mAChR agonist AF267B, the endogenous level of BACE1 decreases via an unclear mechanism, accompanied by a decreased Abeta level[77]. However, another study found that stimulation of M1 mAChR upregulates BACE1 levels in SK-SH-SY5Y cells via the PKC and MAPK signaling cascades[78]. We recently found that M1 mAChR directly interacts with BACE1 and mediates its proteasomal degradation[79]. These results suggest that M1 mAChR modulates BACE1 in a mixed manner. PubMed:24590577

Appears in Networks:

p(HGNC:CHRM1) regulates p(HGNC:BACE1) View Subject | View Object

When APP/PS1/tau triple transgenic (3×Tg) AD mice are treated with the selective M1 mAChR agonist AF267B, the endogenous level of BACE1 decreases via an unclear mechanism, accompanied by a decreased Abeta level[77]. However, another study found that stimulation of M1 mAChR upregulates BACE1 levels in SK-SH-SY5Y cells via the PKC and MAPK signaling cascades[78]. We recently found that M1 mAChR directly interacts with BACE1 and mediates its proteasomal degradation[79]. These results suggest that M1 mAChR modulates BACE1 in a mixed manner. PubMed:24590577

Appears in Networks:

complex(p(HGNC:BACE1), p(HGNC:CHRM1)) hasComponent p(HGNC:BACE1) View Subject | View Object

Appears in Networks:

complex(p(HGNC:BACE1), p(HGNC:CHRM1)) increases deg(p(HGNC:BACE1)) View Subject | View Object

When APP/PS1/tau triple transgenic (3×Tg) AD mice are treated with the selective M1 mAChR agonist AF267B, the endogenous level of BACE1 decreases via an unclear mechanism, accompanied by a decreased Abeta level[77]. However, another study found that stimulation of M1 mAChR upregulates BACE1 levels in SK-SH-SY5Y cells via the PKC and MAPK signaling cascades[78]. We recently found that M1 mAChR directly interacts with BACE1 and mediates its proteasomal degradation[79]. These results suggest that M1 mAChR modulates BACE1 in a mixed manner. PubMed:24590577

Appears in Networks:

act(p(FPLX:PKC)) increases p(HGNC:BACE1) View Subject | View Object

When APP/PS1/tau triple transgenic (3×Tg) AD mice are treated with the selective M1 mAChR agonist AF267B, the endogenous level of BACE1 decreases via an unclear mechanism, accompanied by a decreased Abeta level[77]. However, another study found that stimulation of M1 mAChR upregulates BACE1 levels in SK-SH-SY5Y cells via the PKC and MAPK signaling cascades[78]. We recently found that M1 mAChR directly interacts with BACE1 and mediates its proteasomal degradation[79]. These results suggest that M1 mAChR modulates BACE1 in a mixed manner. PubMed:24590577

Appears in Networks:

p(HGNC:NTRK1) decreases act(p(HGNC:BACE1)) View Subject | View Object

It is also important to note that TrkA reduces and p75NTR activates β-secretase strike (BACE) cleavage of the amyloid precursor protein (APP), which requires NGF binding and activation of the second messenger ceramide [66]. Aging may activate beta-amyloid (Ab) generation in the brain by ‘switching’ from TrkA to p75NTR, suggesting that NGF receptor balance is a molecular link between normal aging of the brain and AD in relation to amyloid processing. PubMed:18986241

Appears in Networks:
Annotations
Disease Ontology (DO)
Alzheimer's disease
MeSH
Cognitive Dysfunction

p(HGNC:NGFR) increases act(p(HGNC:BACE1)) View Subject | View Object

It is also important to note that TrkA reduces and p75NTR activates β-secretase strike (BACE) cleavage of the amyloid precursor protein (APP), which requires NGF binding and activation of the second messenger ceramide [66]. Aging may activate beta-amyloid (Ab) generation in the brain by ‘switching’ from TrkA to p75NTR, suggesting that NGF receptor balance is a molecular link between normal aging of the brain and AD in relation to amyloid processing. PubMed:18986241

Appears in Networks:
Annotations
Disease Ontology (DO)
Alzheimer's disease
MeSH
Cognitive Dysfunction

p(HGNC:ABCA7) decreases p(HGNC:BACE1) View Subject | View Object

However, current evidence showed that ATP-binding cassette transporter A7 deficit can increase Aβ deposition in brain by promoting Aβ-production through increasing β-secretase 1 levels rather than influencing the clearance of Aβ in APP/PS1 mice (Sakae et al. 2016) PubMed:29626319

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p(HGNC:SUMO3) increases p(HGNC:BACE1) 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

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a(CHEBI:Anatabine) decreases p(HGNC:BACE1) View Subject | View Object

Following 24 h of treatment, a dose dependent inhibition of BACE-1 protein levels was observed with anatabine (Fig. 7B) PubMed:21958873

Appears in Networks:
Annotations
Experimental Factor Ontology (EFO)
SH-SY5Y

complex(GO:"NF-kappaB complex") regulates p(HGNC:BACE1) View Subject | View Object

Since BACE-1 transcription is regulated by NFκB (Buggia-Prevot et al., 2008) and since we have shown that anatabine inhibits NFκB activation, we investigated the effect of anatabine on BACE-1 transcription using human neuronal like SH-SY5Y cells PubMed:21958873

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p(HGNC:TNF) increases p(HGNC:BACE1) View Subject | View Object

As expected, TNFα greatly stimulated BACE-1 transcription whereas anatabine fully prevented the increase in BACE-1 mRNA levels induced by TNFα (Fig. 7A). PubMed:21958873

Appears in Networks:
Annotations
Experimental Factor Ontology (EFO)
SH-SY5Y

a(CHEBI:"2-[[7-(3,4-dimethoxyphenyl)-5-imidazo[1,2-c]pyrimidinyl]amino]-3-pyridinecarboxamide") decreases p(HGNC:BACE1) View Subject | View Object

We found that, like (-)-nilvadipine, Syk inhibition with the selective Syk inhibitor BAY61-3606 resulted in decreased sAPPβ secretion, BACE-1 mRNA, and BACE-1 protein expression (data not shown). PubMed:25331948

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a(CHEBI:Nilvadipine) decreases p(HGNC:BACE1) View Subject | View Object

In addition, a reduction in BACE-1 protein levels was observed following treatment of HEK293 cells with (-)-nilvadipine or racemic nilvadipine (Fig. 1D) further suggesting that the inhibition of Aβ production observed following nilvadipine treatment is mediated in part by a reduction of BACE-1 expression. PubMed:25331948

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a(CHEBI:Nilvadipine) decreases p(HGNC:BACE1) View Subject | View Object

As (-)-nilvadipine and racemic nilvadipine inhibit BACE-1 transcription, we evaluated whether (-)-nilvadipine was impacting NFkB activation because NFkB has been shown to play an important role in the regulation of BACE-1 transcription and expression (36, 37, 43, 44) PubMed:25331948

Appears in Networks:

a(CHEBI:Nilvadipine) decreases p(HGNC:BACE1) View Subject | View Object

We found that, like (-)-nilvadipine, Syk inhibition with the selective Syk inhibitor BAY61-3606 resulted in decreased sAPPβ secretion, BACE-1 mRNA, and BACE-1 protein expression (data not shown). PubMed:25331948

Appears in Networks:

complex(GO:"NF-kappaB complex") regulates p(HGNC:BACE1) View Subject | View Object

As (-)-nilvadipine and racemic nilvadipine inhibit BACE-1 transcription, we evaluated whether (-)-nilvadipine was impacting NFkB activation because NFkB has been shown to play an important role in the regulation of BACE-1 transcription and expression (36, 37, 43, 44) PubMed:25331948

Appears in Networks:

act(p(HGNC:SYK)) increases p(HGNC:BACE1) View Subject | View Object

We found that, like (-)-nilvadipine, Syk inhibition with the selective Syk inhibitor BAY61-3606 resulted in decreased sAPPβ secretion, BACE-1 mRNA, and BACE-1 protein expression (data not shown). PubMed:25331948

Appears in Networks:

p(HGNC:TNF) increases p(HGNC:BACE1) View Subject | View Object

Tumor necrosis factor-α (TNFα) has been shown to induce BACE-1 expression and to contribute to brain accumulation of Aβ peptides PubMed:25331948

Appears in Networks:

p(HGNC:TNF) increases p(HGNC:BACE1) View Subject | View Object

We found that both (-)-nilvadipine and racemic nilvadipine reduce BACE-1 mRNA expression (Fig. 1C) induced by TNFα PubMed:25331948

Appears in Networks:

p(HGNC:SYK) regulates p(HGNC:BACE1) View Subject | View Object

Dystrophic neurites are characterized by an accumula- tion of BACE-1 and sAPP β [31] and our previous work [28] has shown that Syk regulates BACE-1 expression and sAPP β levels suggesting that Syk upregulation in dystrophic neurites could contribute to the accumulation of BACE-1 and sAPP β . PubMed:28877763

Appears in Networks:
Annotations
MeSH
Neurites
MeSH
Neurons

g(HGNC:"MIR124-1") decreases p(HGNC:BACE1) View Subject | View Object

Moreover, inhibition of miR‐124 significantly increases the level of BACE1 in neurons. On the other hand, its overexpression significantly suppresses the expression of BACE1. PubMed:30663117

Appears in Networks:
Annotations
MeSH
Neurons
MeSH
Alzheimer Disease

complex(g(HGNC:MIR15B), r(HGNC:BACE1)) decreases p(HGNC:BACE1) View Subject | View Object

The experiments conducted on SH‐SY5Y cells show that computational analyses on the miR‐15b binding site 3′‐UTR can be proven in practice, and miR‐15b expression can reduce BACE1 by binding to this sequence PubMed:30663117

Appears in Networks:
Annotations
Experimental Factor Ontology (EFO)
SH-SY5Y
MeSH
Alzheimer Disease

complex(g(HGNC:MIR339), r(HGNC:BACE1)) decreases p(HGNC:BACE1) View Subject | View Object

For example, miR‐339‐5p, having two binding sites on BCAE1 mRNA, can downregulate the expression of the BACE1 protein PubMed:30663117

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

complex(g(HGNC:MIR384), r(HGNC:BACE1)) decreases p(HGNC:BACE1) View Subject | View Object

It was found that miR‐384, by binding to the 3′‐UTR sequence on BACE1 mRNA, could not only reduce expression in SH‐SY5Y cells but also attach to the 3′‐UTR sequence of the mRNA APP and reduce its expression, and this highlights the importance of miR‐384 in AD PubMed:30663117

Appears in Networks:
Annotations
Experimental Factor Ontology (EFO)
SH-SY5Y
MeSH
Alzheimer Disease

p(HGNC:RELA) increases p(HGNC:BACE1) View Subject | View Object

Our result showed that p65 overexpression significantly increased BACE1 protein level by 232.54¡12.86% (p<0.01 relative to controls) (Fig. 5g). PubMed:21329555

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path(MESH:"Alzheimer Disease") positiveCorrelation p(HGNC:BACE1) View Subject | View Object

BACE1 mRNA levels were also markedly increased in the cortex of AD patients (126.40¡9.01% relative to controls, p<0.05) (Fig. 1b). PubMed:21329555

Appears in Networks:
Annotations
MeSH
Prefrontal Cortex

complex(GO:"NF-kappaB complex") increases p(HGNC:BACE1) View Subject | View Object

A multitude of studies have demonstrated that NF-κB directly regulates the transcription and expression of BACE1, thereby eliciting profound effects on AβPP processing and engenderment of Amyloid-β PubMed:28745240

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

complex(GO:"NF-kappaB complex") increases p(HGNC:BACE1) View Subject | View Object

NF-κB induced up-regulation in BACE1 expression is contingent on the nature of the NF-κB heterodimer PubMed:28745240

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

complex(p(HGNC:BACE1), p(HGNC:NFKB1), p(HGNC:RELA)) hasComponent p(HGNC:BACE1) View Subject | View Object

Appears in Networks:

complex(p(HGNC:BACE1), p(HGNC:NFKB1), p(HGNC:RELA)) increases p(HGNC:BACE1) View Subject | View Object

The binding of p65/p50 or p65/p52 NF- κB heterodimer in the BACE1 promoter results in transcriptional activation whereas the binding of c-Rel/p52 heterodimer results in repression of BACE1 transcription PubMed:28745240

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

complex(p(HGNC:BACE1), p(HGNC:NFKB2), p(HGNC:REL)) hasComponent p(HGNC:BACE1) View Subject | View Object

Appears in Networks:

complex(p(HGNC:BACE1), p(HGNC:NFKB2), p(HGNC:RELA)) hasComponent p(HGNC:BACE1) View Subject | View Object

Appears in Networks:

complex(p(HGNC:BACE1), p(HGNC:NFKB2), p(HGNC:RELA)) increases p(HGNC:BACE1) View Subject | View Object

The binding of p65/p50 or p65/p52 NF- κB heterodimer in the BACE1 promoter results in transcriptional activation whereas the binding of c-Rel/p52 heterodimer results in repression of BACE1 transcription PubMed:28745240

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

complex(p(HGNC:BACE1), p(HGNC:NFKB2), p(HGNC:RELA)) decreases p(HGNC:BACE1) View Subject | View Object

The binding of p65/p50 or p65/p52 NF- κB heterodimer in the BACE1 promoter results in transcriptional activation whereas the binding of c-Rel/p52 heterodimer results in repression of BACE1 transcription PubMed:28745240

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

a(PUBCHEM:155160) decreases act(p(HGNC:BACE1)) View Subject | View Object

It inactivated– and -secretases and astrocytes through the inter-ference of NF-B activation [144 PubMed:29179999

Appears in Networks:

a(PUBCHEM:444795) decreases p(HGNC:BACE1) View Subject | View Object

It reduced BACE1 expression and repressed LPS-activated nuclear translocation of NF-B and its binding to the BACE1 promoter [222]. PubMed:29179999

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act(p(FPLX:NFkappaB)) increases p(HGNC:BACE1) View Subject | View Object

NF-B activation mediates the expression of the pro-oxidant NAPDH oxidase, cyclooxygenase 2 (COX2), interleukins and the antioxidant enzyme, superoxide dismutase (SOD) [78]. Additionally, NF-B activity is associated with the expression of BACE1 [79] and the activation of nucleotide-binding oligomerization domain-like receptor (NALP) 3 inflammosome [80]. PubMed:29179999

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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(MESH:"Anti-Inflammatory Agents, Non-Steroidal") decreases act(p(HGNC:BACE1)) View Subject | View Object

NSAIDs inhibit BACE1 tran- scriptional activation induced by strong NF-κB activator TNF-α. PubMed:27288790

Appears in Networks:
Annotations
MeSH
Cerebral Cortex
MeSH
Hippocampus

complex(a(CHEBI:pentosidine), p(HGNC:AGER)) increases p(HGNC:BACE1) View Subject | View Object

Two AGEs, such as pentosidine and glyceraldehyde derived pyridinium (GLAP), both found increased in AD brains, were able to upregulate BACE1 through their binding with RAGE and consequent activation of NF-κB, providing a pathologic link between diabetes and AD [49]. PubMed:27288790

Appears in Networks:

complex(a(HBP:GLAP), p(HGNC:AGER)) increases p(HGNC:BACE1) View Subject | View Object

Two AGEs, such as pentosidine and glyceraldehyde derived pyridinium (GLAP), both found increased in AD brains, were able to upregulate BACE1 through their binding with RAGE and consequent activation of NF-κB, providing a pathologic link between diabetes and AD [49]. PubMed:27288790

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p(HGNC:GSK3B) increases p(HGNC:BACE1) View Subject | View Object

Stimulation of GSK3β but not GSK3α promoted BACE1 gene expression and BACE1-mediated APP processing in vitro by regulating BACE1 gene promoter activity, which was dependent on NF-κB p65-binding elements in the BACE1 pro- moter [51]. PubMed:27288790

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p(HGNC:GSK3A) causesNoChange p(HGNC:BACE1) View Subject | View Object

Stimulation of GSK3β but not GSK3α promoted BACE1 gene expression and BACE1-mediated APP processing in vitro by regulating BACE1 gene promoter activity, which was dependent on NF-κB p65-binding elements in the BACE1 pro- moter [51]. PubMed:27288790

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p(HGNC:TNF) increases act(p(HGNC:BACE1)) View Subject | View Object

NSAIDs inhibit BACE1 tran- scriptional activation induced by strong NF-κB activator TNF-α. PubMed:27288790

Appears in Networks:
Annotations
MeSH
Cerebral Cortex
MeSH
Hippocampus

p(HGNC:UCHL1) decreases 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:
Annotations
MeSH
Brain
MeSH
Alzheimer Disease

act(p(HGNC:UCHL1)) decreases 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:
Annotations
MeSH
Brain
MeSH
Alzheimer Disease

r(HGNC:"BACE1-AS") regulates p(HGNC:BACE1) View Subject | View Object

BACE1-AS regulates BACE1 mRNA and subsequently BACE1 protein expression in vitro and in vivo. PubMed:27288790

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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

act(complex(GO:"NF-kappaB complex")) 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

act(complex(GO:"NF-kappaB complex")) decreases p(HGNC:BACE1) View Subject | View Object

Under physiological conditions activation of NF-κB by endogenous Aβ reduces βAPP, BACE1 and the γ-secretase activity, thereby lowering Aβ processing and facilitating Aβ homeostasis PubMed:25652642

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Out-Edges 39

p(HGNC:BACE1) hasVariant p(HGNC:BACE1, var("p.?")) View Subject | View Object

Appears in Networks:

p(HGNC:BACE1) increases sec(a(HBP:"sAPP-beta")) View Subject | View Object

Transient transfection of SH-SY5Y APP-695 cells with Asp 2 (Fig. 2a) results in a significant increase in the secretion of sAPPb (Fig. 2b) consistent with Asp 2 being b-secretase. To demonstrate that this increase in sAPPb is linked to the proteolytic activity of Asp 2, we mutated each of the proposed catalytic aspartic residues at positions 25 and 215 (determined by comparison with the position of the known catalytic aspartyl residues in pepsin) to asparagine. Both mutants and the wild-type Asp 2 are expressed to similar levels (Fig. 2a). PubMed:10656250

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Annotations
Experimental Factor Ontology (EFO)
SH-SY5Y

p(HGNC:BACE1) causesNoChange sec(a(HBP:"sAPP-alpha")) View Subject | View Object

However, expression of either of the Asp 2 mutants does not produce the increase in the secretion of sAPPb (Fig. 2b) seen for wild-type Asp 2. In contrast to this clear effect on sAPPb, Asp 2 has no effect on the secretion of soluble APPa or on full-length APP in the cell (data not shown). PubMed:10656250

Appears in Networks:

p(HGNC:BACE1) causesNoChange p(HGNC:APP) View Subject | View Object

However, expression of either of the Asp 2 mutants does not produce the increase in the secretion of sAPPb (Fig. 2b) seen for wild-type Asp 2. In contrast to this clear effect on sAPPb, Asp 2 has no effect on the secretion of soluble APPa or on full-length APP in the cell (data not shown). PubMed:10656250

Appears in Networks:

p(HGNC:BACE1, loc(GO:"endoplasmic reticulum")) association p(HGNC:APP, loc(GO:"endoplasmic reticulum")) View Subject | View Object

APP clearly localizes to the Golgi/endoplasmic reticulum region as revealed by distinctive juxtanuclear staining and a more generalized reticular staining throughout the cell (Figs. 6b and 6g). Asp 2 shows essentially the same subcellular distribution as revealed by simultaneous detection of myc-tagged Asp 2 and APP in COS-7 APP-751 cells (compare Figs. 6f and 6g), and merging of the confocal images for APP and Asp 2 indicates colocalization (Fig. 6h). PubMed:10656250

Appears in Networks:

p(HGNC:BACE1) increases p(HGNC:APP, frag("672_770")) View Subject | View Object

However, while there is a significant increase in the production of CTFb in the presence of wild-type Asp 2, there is no increase in the presence of the mutant enzymes (Fig. 4b). PubMed:10656250

Appears in Networks:

p(HGNC:BACE1) association a(HBP:APP695) View Subject | View Object

Using the same anti-peptide sera we can detect expression of endogenous Asp 2 in SH-SY5Y cells stably expressing the 695 isoform of APP (SH-SY5Y APP-695) and in COS-7 cells expressing the 751 isoform of APP (COS-7 APP-751). The level of Asp 2 is increased upon transient transfection with the protein. PubMed:10656250

Appears in Networks:
Annotations
Experimental Factor Ontology (EFO)
SH-SY5Y

p(HGNC:BACE1) association a(HBP:APP751) View Subject | View Object

Using the same anti-peptide sera we can detect expression of endogenous Asp 2 in SH-SY5Y cells stably expressing the 695 isoform of APP (SH-SY5Y APP-695) and in COS-7 cells expressing the 751 isoform of APP (COS-7 APP-751). The level of Asp 2 is increased upon transient transfection with the protein. PubMed:10656250

Appears in Networks:
Annotations
Experimental Factor Ontology (EFO)
COS-7 cell

act(p(HGNC:BACE1), ma(pep)) increases rxn(reactants(p(HGNC:APP)), products(p(HGNC:APP, frag("11_*")), p(HGNC:APP, frag("1_10")))) View Subject | View Object

BACE1 generates the N terminus of Aβ.In addition,BACE1 can also cleave within the Aβ domain between Tyr 10 and Glu 11. PubMed:18650430

Appears in Networks:
Annotations
Confidence
High

p(HGNC:BACE1) hasVariant p(HGNC:BACE1, frag("228_236")) View Subject | View Object

Appears in Networks:

p(HGNC:BACE1) hasVariant p(HGNC:BACE1, frag("230_235")) View Subject | View Object

Appears in Networks:

p(HGNC:BACE1) hasVariant p(HGNC:BACE1, frag("67_78")) View Subject | View Object

Appears in Networks:

p(HGNC:BACE1) hasVariant p(HGNC:BACE1, frag("69_75")) View Subject | View Object

Appears in Networks:

p(HGNC:BACE1) increases rxn(reactants(p(HGNC:APP)), products(a(CHEBI:"amyloid-beta"))) View Subject | View Object

Abeta is generated from b-amyloid precursor protein (APP) through sequential cleavages first by beta-secretase and then by gamma-secretase complex PubMed:21214928

Appears in Networks:
Annotations
Confidence
Medium

p(HGNC:BACE1) increases rxn(reactants(p(HGNC:APP)), products(a(CHEBI:"amyloid-beta"))) View Subject | View Object

The first step in Abeta generation is cleavage of APP by the beta-secretase PubMed:21214928

Appears in Networks:
Annotations
Confidence
High
MeSH
Neurons

p(HGNC:BACE1) increases rxn(reactants(p(HGNC:APP)), products(a(CHEBI:"amyloid-beta"))) View Subject | View Object

These results provide convincing evidence that BACE1 is the beta-secretase involved in APP metabolism [63-67]; and BACE1 activity is thought to be the rate-limiting factor in Abeta generation from APP PubMed:21214928

Appears in Networks:
Annotations
Confidence
High
MeSH
Neurons

p(HGNC:BACE1) increases bp(GO:"neuron death") 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

p(HGNC:BACE1) decreases bp(GO:"synaptic transmission, cholinergic") 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

p(HGNC:BACE1) decreases bp(GO:memory) 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

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

p(HGNC:BACE1) increases p(HGNC:APP, frag("672_711")) 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

p(HGNC:BACE1) increases rxn(reactants(p(HGNC:APP)), products(a(CHEBI:"amyloid-beta"))) View Subject | View Object

The processing of APP to generate Abeta is executed by beta- and gamma-secretase and is highly regulated PubMed:22122372

Appears in Networks:
Annotations
Confidence
Medium

p(HGNC:BACE1) increases rxn(reactants(p(HGNC:APP)), products(a(HBP:HBP00042), a(HBP:HBP00081))) View Subject | View Object

In the amyloidogenic pathway, APP is primarily processed by beta-secretase at the first residue or at the 11th residue (so called beta’ site) of the Abeta peptide sequence (Fig. 1), shedding sAPPbeta and generating a membrane associated C-terminal fragment consisting of 99 amino acids (C99) (Sarah and Robert 2007) PubMed:22122372

Appears in Networks:
Annotations
Confidence
High
MeSH
Neurons

p(HGNC:BACE1) increases rxn(reactants(p(HGNC:APP)), products(a(HBP:HBP00042), a(HBP:HBP00081))) View Subject | View Object

Abeta generation is initiated by beta-cleavage at the ectodomain of APP, resulting in the generation of an sAPP-beta domain and the membrane associated APP C-terminal fragment C99. The putative beta-secretase, beta-site APP cleaving enzyme 1 (BACE1), was first identified and characterized in 1999 (Sinha et al. 1999; Vassar et al. 1999; Yan et al. 1999; Hussain et al. 2000; Lin et al. 2000). PubMed:22122372

Appears in Networks:
Annotations
Confidence
High
MeSH
Neurons

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

Knocking out the BACE1 gene prevents Abeta generation and completely abolishes Abeta pathology in mice expressing the Swedish mutation of human APP (Cai et al. 2001; Luo et al. 2001; Roberds et al. 2001; Ohno et al. 2004; Laird et al. 2005) PubMed:22122372

Appears in Networks:
Annotations
Confidence
High
MeSH
Neurons

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

Appears in Networks:
Annotations
Text Location
Review

p(HGNC:BACE1) increases deg(p(HGNC:APP)) View Subject | View Object

Abeta, an important player in AD, is derived from beta-amyloid precursor protein (APP) through sequential cleavages by beta- and gamma-secretases: APP is cleaved by beta-secretase (BACE1) to generate the large secreted derivative sAPPbeta and the membrane-bound APP C-terminal fragment-beta; the latter can be further cleaved by gamma-secretase to generate Abeta and APP intracellular domain. Alternatively, APP can be cleaved by alpha-secretase within the Abeta domain, which precludes Abeta production and instead generates secreted sAPPalpha that has been shown to be neuroprotective PubMed:24590577

Appears in Networks:

p(HGNC:BACE1) increases a(HBP:"sAPP-beta") View Subject | View Object

Abeta, an important player in AD, is derived from beta-amyloid precursor protein (APP) through sequential cleavages by beta- and gamma-secretases: APP is cleaved by beta-secretase (BACE1) to generate the large secreted derivative sAPPbeta and the membrane-bound APP C-terminal fragment-beta; the latter can be further cleaved by gamma-secretase to generate Abeta and APP intracellular domain. Alternatively, APP can be cleaved by alpha-secretase within the Abeta domain, which precludes Abeta production and instead generates secreted sAPPalpha that has been shown to be neuroprotective PubMed:24590577

Appears in Networks:

p(HGNC:BACE1) increases a(HBP:C99) View Subject | View Object

Abeta, an important player in AD, is derived from beta-amyloid precursor protein (APP) through sequential cleavages by beta- and gamma-secretases: APP is cleaved by beta-secretase (BACE1) to generate the large secreted derivative sAPPbeta and the membrane-bound APP C-terminal fragment-beta; the latter can be further cleaved by gamma-secretase to generate Abeta and APP intracellular domain. Alternatively, APP can be cleaved by alpha-secretase within the Abeta domain, which precludes Abeta production and instead generates secreted sAPPalpha that has been shown to be neuroprotective PubMed:24590577

Appears in Networks:

p(HGNC:BACE1) decreases p(HGNC:APP) 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

Appears in Networks:
Annotations
Confidence
Medium

p(HGNC:BACE1) increases a(CHEBI:"amyloid-beta polypeptide 40") 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

Appears in Networks:
Annotations
Confidence
Medium

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

It is also important to note that TrkA reduces and p75NTR activates β-secretase strike (BACE) cleavage of the amyloid precursor protein (APP), which requires NGF binding and activation of the second messenger ceramide [66]. Aging may activate beta-amyloid (Ab) generation in the brain by ‘switching’ from TrkA to p75NTR, suggesting that NGF receptor balance is a molecular link between normal aging of the brain and AD in relation to amyloid processing. PubMed:18986241

Appears in Networks:
Annotations
Disease Ontology (DO)
Alzheimer's disease
MeSH
Cognitive Dysfunction

p(HGNC:BACE1) increases rxn(reactants(p(HGNC:APP)), products(a(MESH:"Amyloid beta-Peptides"))) 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

Appears in Networks:

act(p(HGNC:BACE1)) increases a(HBP:"amyloid-beta derived diffusible ligands") View Subject | View Object

If APP is first cleaved by β-secretase 1 (also known as BACE1) instead of α-secretase, the subsequent γ-secretase cleavage will result in soluble monomeric Aβ. PubMed:26195256

Appears in Networks:

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

Under normal conditions, Aβ production in brain parenchyma results from hydrolyzing amyloid precursor proteins via beta-secreted enzymes and gamma-secreted enzymes, and the most common subtypes of Aβ in human body are Aβ1–40 and Aβ1–42 PubMed:29626319

Appears in Networks:

p(HGNC:BACE1) increases rxn(reactants(p(HGNC:APP)), products(a(CHEBI:"amyloid-beta polypeptide 42"), p(HBP:"APP C-terminally truncated carboxyl-terminal fragments"))) View Subject | View Object

The formation of Aβ starts by a transmembrane protein, APP (695 to 770 amino acids in length), which is sequentially cleaved by the aspartate proteases β- and γ-secretase, that leads to the formation of Aβ peptide (1-42) and a degenerated C-terminus. PubMed:30444369

Appears in Networks:

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

Aβ peptides originate from the transmembrane protein amyloid precursor protein (APP) which undergoes sequential cleavage via two distinct pathways by the enzyme complexes β- and γ-secretase [31] PubMed:29758300

Appears in Networks:

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

In addition, a reduction in BACE-1 protein levels was observed following treatment of HEK293 cells with (-)-nilvadipine or racemic nilvadipine (Fig. 1D) further suggesting that the inhibition of Aβ production observed following nilvadipine treatment is mediated in part by a reduction of BACE-1 expression. PubMed:25331948

Appears in Networks:

p(HGNC:BACE1) positiveCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

BACE1 mRNA levels were also markedly increased in the cortex of AD patients (126.40¡9.01% relative to controls, p<0.05) (Fig. 1b). PubMed:21329555

Appears in Networks:
Annotations
MeSH
Prefrontal Cortex

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.