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A role for APP in Wnt signalling links synapse loss with β-amyloid production. 1.0.0

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charles.hoyt@scai.fraunhofer.de at 2019-02-27 16:04:37.991141
Authors
Esther Wollert
Contact
charles.hoyt@scai.fraunhofer.de
License
CC BY 4.0
Copyright
Copyright © 2018 Fraunhofer Institute SCAI, All rights reserved.
Number Nodes
22
Number Edges
60
Number Components
1
Network Density
0.12987012987013
Average Degree
2.72727272727273
Number Citations
1
Number BEL Errors
0

Content Statistics

Network Overlap

The node-based overlap between this network and other networks is calculated as the Szymkiewicz-Simpson coefficient of their respective nodes. Up to the top 10 are shown below.

Network Overlap
Effects of peptides derived from BACE1 catalytic domain on APP processing v1.0.0 20%
Tau Modifications v1.9.5 18%
The Spleen Tyrosine Kinase (Syk) Regulates Alzheimer Amyloid-β Production and Tau Hyperphosphorylation* v1.0.0 14%
APP processing in Alzheimer's disease v1.0.1 14%
Proteolytic processing of Alzeimer's beta-amyloid precursor protein v1.0.1 14%
Tau in physiology and pathology v1.0.0 14%
Nicotinic acetylcholine receptor signalling: roles in Alzheimer's disease and amyloid neuroprotection. v1.0.0 14%
Role of the nicotinic acetylcholine receptor in Alzheimer's disease pathology and treatment v1.0.1 14%
Nuclear receptors as therapeutic targets for Alzheimer's disease. v1.0.0 14%
Nicotinic Receptor Abnormalities of Alzheimer’s Disease: Therapeutic Implications v1.0.0 14%

Sample Edges

a(CHEBI:"amyloid-beta") increases bp(HBP:HBP00061) View Subject | View Object

Aβ synaptoxicity is Dkk1-dependent12,24 and also appears to be APP-dependent25. PubMed:30232325

Annotations
Confidence
High

a(CHEBI:"fasudil hydrochloride") decreases bp(GO:"Wnt signaling pathway, planar cell polarity pathway") View Subject | View Object

The Wnt-PCP signalling pathway acts through RhoA and ROCK26, and can be inhibited pharmacologically, for example, with fasudil24, a ROCK inhibitor that is in clinical use for the treatment of cerebral vasospasm. PubMed:30232325

Annotations
Confidence
High

a(CHEBI:"fasudil hydrochloride") decreases a(CHEBI:"amyloid-beta polypeptide 40") View Subject | View Object

Fasudil also reversed the stimulatory effect of Vangl2 and Dkk1 on Aβ production in the same cells as determined by ELISA based quantification of Aβ1–40 levels in the paired culture media from the same experiments (Fig. 3d). PubMed:30232325

Annotations
Confidence
High

a(CHEBI:"fasudil hydrochloride") decreases a(CHEBI:"amyloid-beta polypeptide 40") View Subject | View Object

Animals receiving fasudil had significantly lower soluble Aβ1–40 levels than controls (Fig. 4b). PubMed:30232325

Annotations
Confidence
High

bp(GO:"Wnt signaling pathway, planar cell polarity pathway") association p(HGNC:VANGL2) View Subject | View Object

APP has previously been shown to interact with Vangl2, a Wnt-PCP-specific co-receptor protein, and independently has been shown to bind LRP6, a receptor component of the Wnt-β-catenin pathway21. PubMed:30232325

Annotations
Confidence
High

Sample Nodes

a(CHEBI:"amyloid-beta")

In-Edges: 423 | Out-Edges: 245 | Children: 5 | Explore Neighborhood | Download JSON

a(CHEBI:"amyloid-beta polypeptide 40")

In-Edges: 23 | Out-Edges: 5 | Classes: 1 | Explore Neighborhood | Download JSON

a(CHEBI:"fasudil hydrochloride")

In-Edges: 1 | Out-Edges: 3 | Explore Neighborhood | Download JSON

a(MESH:"Dendritic Spines")

In-Edges: 23 | Out-Edges: 5 | Explore Neighborhood | Download JSON

bp(GO:"Wnt signaling pathway, planar cell polarity pathway")

In-Edges: 7 | Out-Edges: 3 | Explore Neighborhood | Download JSON

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.