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a(HBP:HBP00018)

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Entity

Name
HBP00018
Namespace
HBP
Namespace Version
20181029
Namespace URL
https://raw.githubusercontent.com/pharmacome/terminology/785431732a26d6809b4162d98b95687d16404e63/export/hbp.belns

Appears in Networks 10

Functional aspects of meningeal lymphatics in ageing and Alzheimer’s disease v1.0.0

Amyloid β oligomers (AβOs) in Alzheimer’s disease 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

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

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

Chaperoning α7 neuronal nicotinic acetylcholine receptors v1.0.0

Alpha-synuclein oligomers: a new hope v1.0.0

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

Progress and Developments in Tau Aggregation Inhibitors for Alzheimer Disease v0.1.0

A small assortment of academic articles describing quantitatively described interactions between the MAPT (Tau) protein and small molecules

In-Edges 35

act(a(MESH:"Lymphatic Vessels")) decreases a(HBP:HBP00018) View Subject | View Object

A similar outcome was observed in J20 transgenic mice after a total of three months of meningeal lymphatic ablation (Extended Data Fig. 9f); amyloid-β aggregates had formed in the meninges (Extended Data Fig. 9g) and the amyloid-β plaque load in the hippocampi of these mice was significantly increased (Extended Data Fig. 9h–k) PubMed:30046111

Appears in Networks:
Annotations
Confidence
High
MeSH
Meninges

path(MESH:"Alzheimer Disease") positiveCorrelation a(HBP:HBP00018) View Subject | View Object

Extracellular deposition of amyloid-β aggregates, the main constituent of senile plaques, is considered to be a pathological hallmark of Alzheimer’s disease that contributes to neuronal dysfunction and behavioural changes PubMed:30046111

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Extracellular Space

p(HGNC:APBA1) decreases a(HBP:HBP00018) View Subject | View Object

Overexpression of Mint1, Mint2, or Fe65 causes reduction in Aβ generation and deposition in the brains of transgenic mice, strongly suggesting a physiological role for these adaptors in regulating APP processing in the nervous tis- sue (17). PubMed:18650430

Appears in Networks:
Annotations
Confidence
Medium

p(HGNC:APBA2) decreases a(HBP:HBP00018) View Subject | View Object

Overexpression of Mint1, Mint2, or Fe65 causes reduction in Aβ generation and deposition in the brains of transgenic mice, strongly suggesting a physiological role for these adaptors in regulating APP processing in the nervous tis- sue (17). PubMed:18650430

Appears in Networks:
Annotations
Confidence
Medium

p(HGNC:APBB1) decreases a(HBP:HBP00018) View Subject | View Object

Overexpression of Mint1, Mint2, or Fe65 causes reduction in Aβ generation and deposition in the brains of transgenic mice, strongly suggesting a physiological role for these adaptors in regulating APP processing in the nervous tis- sue (17). PubMed:18650430

Appears in Networks:
Annotations
Confidence
Medium

path(MESH:"Down Syndrome") increases a(HBP:HBP00018) View Subject | View Object

As DS also results in Abeta accumulation, the genes location suggests a link between BACE2 and APP processing PubMed:21214928

Appears in Networks:
Annotations
MeSH
Endosomes
Confidence
Medium
MeSH
Neurons

a(CHEBI:"amyloid-beta") increases a(HBP:HBP00018) View Subject | View Object

gamma-Secretase further cleaves C99 to release AICD and the amyloidogenic Abeta peptide which aggregates and fibrillates to form amyloid plaques in the brain PubMed:22122372

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Neurons

a(MESH:"Amyloid beta-Peptides") association a(HBP:HBP00018) View Subject | View Object

The amyloid plaques associated with AD were first purified and found to consist of multimeric aggregates of Abeta polypeptide containing about 40 amino acid residues in the mid-1980s (Glenner and Wong 1984; Masters et al. 1985) PubMed:22122372

Appears in Networks:
Annotations
Confidence
High
MeSH
Cerebral Cortex
MeSH
Hippocampus

a(CHEBI:"GW 3965") decreases a(HBP:HBP00018) View Subject | View Object

Significantly, a 4-month treatment of Tg2576 mice with GW3965 reduced plaque deposition by > 50% and improved contextual memory in these animals [13]. PubMed:21718217

Appears in Networks:
Annotations
Confidence
High

a(CHEBI:"GW 501516") decreases a(HBP:HBP00018) View Subject | View Object

In a study reported by Kalinin et al., treatment of 5xFAD mice with the PPAR-d agonist, GW742, resulted in decreased plaque burden and an increase in the expression of two Ab proteases, neprilysin and IDE [72]. PubMed:21718217

Appears in Networks:
Annotations
Confidence
High

a(CHEBI:"all-trans-retinoic acid") decreases a(HBP:HBP00018) View Subject | View Object

Treatment of 5-month-old APP/PS1 mice for 8 weeks with ATRA (20 mg/kg/day) resulted in significant decreases in Ab deposition and tau phosphorylation in these mice. Additionally, it attenuated memory deficits seen in the Morris water maze [77]. PubMed:21718217

Appears in Networks:
Annotations
Confidence
Medium

a(CHEBI:bexarotene) decreases a(HBP:HBP00018) 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

a(CHEBI:pioglitazone) decreases a(HBP:HBP00018) 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

Appears in Networks:
Annotations
Confidence
High

a(CHEBI:pioglitazone) decreases a(HBP:HBP00018) View Subject | View Object

Furthermore, the treatment of APP/PS1 mouse model of AD with pioglitazone (80 mg/kg/day) for 9 days lowered plaque burden by ~ 50% and reversed behavioral deficits in contextual fear conditioning assay. PubMed:21718217

Appears in Networks:
Annotations
Confidence
High

a(CHEBI:rosiglitazone) causesNoChange a(HBP:HBP00018) 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

Appears in Networks:
Annotations
Confidence
High

a(CHEBI:rosiglitazone) decreases a(HBP:HBP00018) View Subject | View Object

These animals were treated with a low dose of rosiglitazone (3 mg/kg/ day) for 12 weeks and evaluated for plaque deposition and behavior. These animals displayed an approximate 50% decrease in amyloid deposition, a decrease in Ab oligomers, preservation of pre and postsynaptic proteins and the attenuation of cognitive deficits in the Morris water maze. PubMed:21718217

Appears in Networks:
Annotations
Confidence
High

a(HBP:HBP00030) increases a(HBP:HBP00018) View Subject | View Object

Mice expressing the ApoE4 isoform exhibited higher levels of Ab deposition in comparison to ApoE3 or ApoE2 expressing animals [36]. PubMed:21718217

Appears in Networks:
Annotations
Confidence
High
MeSH
Microglia

p(HGNC:ABCA1) decreases a(HBP:HBP00018) 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

path(MESH:"Alzheimer Disease") association a(HBP:HBP00018) View Subject | View Object

AD is a chronic neurodegenerative disease characterized by the progressive deposition of the amyloid b (Ab) in the parenchyma of the brain. PubMed:21718217

Appears in Networks:
Annotations
Confidence
High

path(MESH:"Alzheimer Disease") increases a(HBP:HBP00018) View Subject | View Object

Another important event that associates well with the Alzheimer disease pathology is the aggregation of the β-amyloid peptide [53]. This peptide interacts with α7 AChRs and has been reported to affect the nor- mal functioning of the latter, causing reduced neuronal survival [146,192–194]. PubMed:22040696

Appears in Networks:
Annotations
MeSH
Hippocampus

a(CHEBI:"(-)-epigallocatechin 3-gallate") decreases a(HBP:HBP00018) View Subject | View Object

Epigallocatechin-3-gallate (EGCG), a small molecule that been shown to inhibit the aggregation of several amyloidogenic proteins such as a-syn, amyloid-beta and huntingtin [9, 37, 38, 105] binds to unfolded native amyloid-beta and a-syn and promotes the formation of nontoxic oligomers that do not convert into amyloid fibrils [37]. PubMed:28803412

Appears in Networks:
Annotations
Confidence
High
MeSH
Brain
MeSH
Cerebrospinal Fluid
MeSH
Serum

a(CHEBI:curcumin) decreases a(HBP:HBP00018) View Subject | View Object

In vitro studies have shown that curcumin inhibited the formation of fibrils and disaggregated amyloid-beta and a-syn [112, 114, 155]. PubMed:28803412

Appears in Networks:
Annotations
Confidence
High
MeSH
Brain
MeSH
Cerebrospinal Fluid
MeSH
Serum

a(CHEBI:"alpha,alpha-trehalose") decreases a(HBP:HBP00018) View Subject | View Object

It also proved effective in cellu- lar models of PD, HD and AD 121,122 , as well as in mouse models of HD, AD and tauopathies, where it cleared aggregates, reduced neurodegeneration and ameliorated motor and cognitive performance 123–125 . PubMed:30116051

Appears in Networks:
Annotations
MeSH
Dopaminergic Neurons

a(CHEBI:fisetin) decreases a(HBP:HBP00018) View Subject | View Object

Moreover, the flavonol fisetin stimulated auto- phagic degradation of phosphorylated tau in cortical neu- rons via mTORC1-dependent activation of TFEB and the cytoprotective transcription factor nuclear factor eryth- roid 2-related factor 2 (NFE2L2) 149 . Fisetin also reduced Aβ accumulation in an APP/PS1 mouse model of AD 150 . PubMed:30116051

Appears in Networks:
Annotations
MeSH
Dopaminergic Neurons
MeSH
Machado-Joseph Disease

a(HBP:HBP00021) decreases a(HBP:HBP00018) View Subject | View Object

Structures of Aβ-aggregation inhibitors evaluated in current or past clinical trials. PubMed:23484434

Appears in Networks:

p(HGNC:GRN) decreases a(HBP:HBP00018) View Subject | View Object

Furthermore, expression of progranulin in the hippocampus of AD mice reduces the density of amyloid plaques by enhanc- ing the activity of neprilysin 281 . PubMed:30116051

Appears in Networks:

p(HGNC:IDE) decreases a(HBP:HBP00018) View Subject | View Object

Aβ42 and amylin (a pancreas-derived, AD-associated protein found in brain) are substrates for degradation by IDE, which also irreversibly traps Aβ42 and α-synuclein, preventing their aggregation and promoting ALN and UPS elimination 259 . PubMed:30116051

Appears in Networks:

p(HGNC:TFEB) decreases a(HBP:HBP00018) View Subject | View Object

Indeed, TFEB over- expression reduced amyloid plaques in a APP/PS1 mouse model 148 . PubMed:30116051

Appears in Networks:
Annotations
MeSH
Dopaminergic Neurons
MeSH
Machado-Joseph Disease

a(CHEBI:10642) decreases a(HBP:HBP00018) View Subject | View Object

Structures of Aβ-aggregation inhibitors evaluated in current or past clinical trials. PubMed:23484434

Appears in Networks:

a(CHEBI:1457) decreases a(HBP:HBP00018) View Subject | View Object

Structures of Aβ-aggregation inhibitors evaluated in current or past clinical trials. PubMed:23484434

Appears in Networks:

a(HBP:HBP00019) decreases a(HBP:HBP00018) View Subject | View Object

Structures of Aβ-aggregation inhibitors evaluated in current or past clinical trials. PubMed:23484434

Appears in Networks:

a(CHEBI:3441) decreases a(HBP:HBP00018) View Subject | View Object

Representative examples of N-phenylamine Tau aggregation inhibitors and structural overlap with the Aβ40 aggregation inhibitor 33 or the nonsteroidal anti-inflammatory drug 34. PubMed:23484434

Appears in Networks:

a(CHEBI:4806) decreases a(HBP:HBP00018) View Subject | View Object

Structures of Aβ-aggregation inhibitors evaluated in current or past clinical trials. PubMed:23484434

Appears in Networks:

a(CHEBI:6710) decreases a(HBP:HBP00018) View Subject | View Object

Representative examples of N-phenylamine Tau aggregation inhibitors and structural overlap with the Aβ40 aggregation inhibitor 33 or the nonsteroidal anti-inflammatory drug 34. PubMed:23484434

Appears in Networks:

a(CHEBI:74460) decreases a(HBP:HBP00018) View Subject | View Object

Structures of Aβ-aggregation inhibitors evaluated in current or past clinical trials. PubMed:23484434

Appears in Networks:

Out-Edges 8

a(HBP:HBP00018) positiveCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

Extracellular deposition of amyloid-β aggregates, the main constituent of senile plaques, is considered to be a pathological hallmark of Alzheimer’s disease that contributes to neuronal dysfunction and behavioural changes PubMed:30046111

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Extracellular Space

a(HBP:HBP00018) decreases bp(GO:"neuron cellular homeostasis") View Subject | View Object

Extracellular deposition of amyloid-β aggregates, the main constituent of senile plaques, is considered to be a pathological hallmark of Alzheimer’s disease that contributes to neuronal dysfunction and behavioural changes PubMed:30046111

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Extracellular Space

a(HBP:HBP00018) increases path(MESH:"Problem Behavior") View Subject | View Object

Extracellular deposition of amyloid-β aggregates, the main constituent of senile plaques, is considered to be a pathological hallmark of Alzheimer’s disease that contributes to neuronal dysfunction and behavioural changes PubMed:30046111

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Extracellular Space

a(HBP:HBP00018) causesNoChange bp(GO:"neuron death") View Subject | View Object

On the contrary, no relationship between total Aβ plaque burden and number of astrocytes or neurons was found (da Rocha-Souto et al. 2011). PubMed:29196815

Appears in Networks:
Annotations
MeSH
Extracellular Space
Cell Ontology (CL)
neuron
Confidence
High

a(HBP:HBP00018) causesNoChange bp(GO:"astrocyte activation") View Subject | View Object

On the contrary, no relationship between total Aβ plaque burden and number of astrocytes or neurons was found (da Rocha-Souto et al. 2011). PubMed:29196815

Appears in Networks:
Annotations
MeSH
Extracellular Space
Cell Ontology (CL)
neuron
Confidence
High

a(HBP:HBP00018) association a(MESH:"Amyloid beta-Peptides") View Subject | View Object

The amyloid plaques associated with AD were first purified and found to consist of multimeric aggregates of Abeta polypeptide containing about 40 amino acid residues in the mid-1980s (Glenner and Wong 1984; Masters et al. 1985) PubMed:22122372

Appears in Networks:
Annotations
Confidence
High
MeSH
Cerebral Cortex
MeSH
Hippocampus

a(HBP:HBP00018) increases path(MESH:"Plaque, Amyloid") View Subject | View Object

gamma-Secretase further cleaves C99 to release AICD and the amyloidogenic Abeta peptide which aggregates and fibrillates to form amyloid plaques in the brain PubMed:22122372

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Neurons

a(HBP:HBP00018) association path(MESH:"Alzheimer Disease") View Subject | View Object

AD is a chronic neurodegenerative disease characterized by the progressive deposition of the amyloid b (Ab) in the parenchyma of the brain. PubMed:21718217

Appears in Networks:
Annotations
Confidence
High

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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.