Repository of proposed pathways and protein-protein interaction networks in age-related macular degeneration
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- dc.contributor.author Pool, Fran M.
- dc.contributor.author Kiel, Christina
- dc.contributor.author Serrano Pubull, Luis, 1982-
- dc.contributor.author Luthert, Philip J.
- dc.date.accessioned 2020-04-27T10:21:42Z
- dc.date.available 2020-04-27T10:21:42Z
- dc.date.issued 2020
- dc.description.abstract Age-related macular degeneration (AMD) is one of the commonest causes of sight loss in the elderly population and to date there is no intervention that slows or prevents early AMD disease progressing to blinding neovascularization or geographic atrophy. AMD is a complex disease and factors proposed to contribute to the development and progression of disease include aging, genetics, epigenetics, oxidative stress, pro-inflammatory state, and life-style factors such as smoking, alcohol, and high fat diet. Here, we generate a knowledge repository of pathways and protein-protein interaction (PPI) networks likely to be implicated in AMD pathogenesis, such as complement activation, lipid trafficking and metabolism, vitamin A cycle, oxidative stress, proteostasis, bioenergetics, autophagy/mitophagy, extracellular matrix (ECM) turnover, and choroidal vascular dropout. Two disctinct clusters ermerged from the networks for parainflamation and ECM homeostasis, which may represent two different disease modules underlying AMD pathology. Our analyses also suggest that the disease manifests primarily in RPE/choroid and less in neural retina. The use of standardized syntax when generating maps of these biological processes (SBGN standard) and networks (PSI standard) enables visualization of complex information in graphical programs such as CellDesigner and Cytoscape and enhances reusability and extension of data. The ability to focus onto subnetworks, multiple visualizations and simulation options will enable the AMD research community to computationally model subnetworks or to test experimentally new hypotheses arising from connectivities in the AMD pathway map.
- dc.description.sponsorship This work has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No. 634479 (EYE-RISK—to P.J.L., L.S., and C.K.). This work was supported by the Spanish Ministry of Economy and Competitiveness, Plan Nacional BIO2012-39754 and the European Fund for Regional Development (to L.S.). L.S. acknowledges the support of the Spanish Ministry of Economy and Competitiveness, “Centro de Excelencia Severo Ochoa 2013–2017” (SEV-2012-0208)
- dc.format.mimetype application/pdf
- dc.identifier.citation Pool FM, Kiel C, Serrano L, Luthert P. Repository of proposed pathways and protein-protein interaction networks in age-related macular degeneration. NPJ Aging Mech Dis. 2020 Jan 7; 6: 2. DOI: 10.1038/s41514-019-0039-5
- dc.identifier.doi http://dx.doi.org/10.1038/s41514-019-0039-5
- dc.identifier.issn 2056-3973
- dc.identifier.uri http://hdl.handle.net/10230/44341
- dc.language.iso eng
- dc.publisher Nature Research
- dc.relation.ispartof NPJ Aging and Mechanisms of Disease. 2020 Jan 7;6:2
- dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/634479
- dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/BIO2012-39754
- dc.rights © 2020 Fran M. Pool et al. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made
- dc.rights.accessRights info:eu-repo/semantics/openAccess
- dc.subject.other Envelliment
- dc.subject.other Proteïnes
- dc.title Repository of proposed pathways and protein-protein interaction networks in age-related macular degeneration
- dc.type info:eu-repo/semantics/article
- dc.type.version info:eu-repo/semantics/publishedVersion