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a(HBP:HBP00038)

Equivalencies: 0 | Classes: 0 | Children: 0 | Explore

Entity

Name
HBP00038
Namespace
HBP
Namespace Version
20181221
Namespace URL
https://raw.githubusercontent.com/pharmacome/terminology/bd0996a28201cad363557315043c6392e31abf58/export/hbp.belns

Appears in Networks 5

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

Inflammasome activation and innate immunity in Alzheimer’s disease v1.0.2

The role of inflammasome in Alzheimer’s disease v1.0.3

In-Edges 6

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

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

Appears in Networks:
Annotations
MeSH
Endosomes
Confidence
Medium
MeSH
Neurons

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

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

Appears in Networks:
Annotations
MeSH
Endosomes
Confidence
High
MeSH
Neurons

a(CHEBI:"amyloid-beta") increases a(HBP:HBP00038) 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

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

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

Appears in Networks:
Annotations
Confidence
High
MeSH
Neurons

a(CHEBI:"GW 3965") increases act(a(HBP:HBP00038)) View Subject | View Object

Similarly, stimulation of microglia with the LXR agonist, GW3965, acts simultaneously to suppress inflammation and promote fibrillar Ab stimulated phagocytosis [47]. PubMed:21718217

Appears in Networks:
Annotations
Confidence
Medium

p(MGI:Abca1) decreases a(HBP:HBP00038) View Subject | View Object

Conversely, overexpression of ABCA1 in a mouse model of AD was shown to decrease both soluble and fibrillar pools of Ab in 12-month-old mice and reduce plaque burden [53]. PubMed:21718217

Appears in Networks:
Annotations
Confidence
Medium

Out-Edges 6

a(HBP:HBP00038) 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:HBP00038) increases p(HGNC:CCL2) View Subject | View Object

The deposition of fibrillar Ab in the AD brain results in the recruitment of microglia to the plaques owing to their expression of CCL2, which acts to attract microglia [82]. PubMed:21718217

Appears in Networks:
Annotations
Confidence
Medium

a(HBP:HBP00038) increases bp(GO:"microglial cell activation") View Subject | View Object

The deposition of fibrillar Ab in the AD brain results in the recruitment of microglia to the plaques owing to their expression of CCL2, which acts to attract microglia [82]. PubMed:21718217

Appears in Networks:
Annotations
Confidence
Medium

act(a(HBP:HBP00038)) increases bp(GO:phagocytosis) View Subject | View Object

Similarly, stimulation of microglia with the LXR agonist, GW3965, acts simultaneously to suppress inflammation and promote fibrillar Ab stimulated phagocytosis [47]. PubMed:21718217

Appears in Networks:
Annotations
Confidence
Medium

a(HBP:HBP00038) increases act(complex(GO:"NLRP3 inflammasome complex")) View Subject | View Object

Activation of the NLRP3 inflammasome by fibrillar Abeta has been described first by Halle et al. in 2008 PubMed:28019679

Appears in Networks:
Annotations
Confidence
High
NeuroMMSigDB
Amyloidogenic subgraph

a(HBP:HBP00038) increases act(complex(GO:"NLRP3 inflammasome complex")) View Subject | View Object

In vivo and cell studies demonstrate that fibrillar Aβ activates the NLRP3 inflammasome which is composed of the NLRP3 receptor, ASC and caspase-1, to produce IL-1β in microglia (Halle et al., 2008) PubMed:24561250

Appears in Networks:
Annotations
Cell Ontology (CL)
microglial cell
Confidence
Medium
NeuroMMSigDB
Amyloidogenic subgraph

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.