Dataset Information

Mizuno2012 - AlzPathway: a comprehensive map of Alzheimer's disease

ABSTRACT: Mizuno2012 - AlzPathway: a comprehensive map of Alzheimer's disease Non-kinetic molecular map. Pure SBML file of AlzPathway provided by the authors as Additional file 5. This model is described in the article: AlzPathway: a comprehensive map of signaling pathways of Alzheimer's disease. Mizuno S, Iijima R, Ogishima S, Kikuchi M, Matsuoka Y, Ghosh S, Miyamoto T, Miyashita A, Kuwano R, Tanaka H. BMC Syst Biol 2012; 6: 52 Abstract: BACKGROUND: Alzheimer's disease (AD) is the most common cause of dementia among the elderly. To clarify pathogenesis of AD, thousands of reports have been accumulating. However, knowledge of signaling pathways in the field of AD has not been compiled as a database before. DESCRIPTION: Here, we have constructed a publicly available pathway map called "AlzPathway" that comprehensively catalogs signaling pathways in the field of AD. We have collected and manually curated over 100 review articles related to AD, and have built an AD pathway map using CellDesigner. AlzPathway is currently composed of 1347 molecules and 1070 reactions in neuron, brain blood barrier, presynaptic, postsynaptic, astrocyte, and microglial cells and their cellular localizations. AlzPathway is available as both the SBML (Systems Biology Markup Language) map for CellDesigner and the high resolution image map. AlzPathway is also available as a web service (online map) based on Payao system, a community-based, collaborative web service platform for pathway model curation, enabling continuous updates by AD researchers. CONCLUSIONS: AlzPathway is the first comprehensive map of intra, inter and extra cellular AD signaling pathways which can enable mechanistic deciphering of AD pathogenesis. The AlzPathway map is accessible at http://alzpathway.org/. This model is hosted on BioModels Database and identified by: MODEL1504290001. To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

SUBMITTER: Audald Lloret i Villas

PROVIDER: MODEL1504290001 | BioModels | 2016-05-09

REPOSITORIES: BioModels

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AlzPathway: a comprehensive map of signaling pathways of Alzheimer's disease.

Mizuno Satoshi S Iijima Risa R Ogishima Soichi S Kikuchi Masataka M Matsuoka Yukiko Y Ghosh Samik S Miyamoto Tadashi T Miyashita Akinori A Kuwano Ryozo R Tanaka Hiroshi H

BMC systems biology 20120530

<h4>Background</h4>Alzheimer's disease (AD) is the most common cause of dementia among the elderly. To clarify pathogenesis of AD, thousands of reports have been accumulating. However, knowledge of signaling pathways in the field of AD has not been compiled as a database before.<h4>Description</h4>Here, we have constructed a publicly available pathway map called "AlzPathway" that comprehensively catalogs signaling pathways in the field of AD. We have collected and manually curated over 100 revie ...[more]

PMID: 22647208

Publication: 1/107

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Project description:Alzheimer's disease (AD) is a chronic neurodegenerative disorder characterized by progressive deterioration of cognitive function. Evidence suggests a role for epigenetic regulation, in particular the cytosine modifications 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC,) in AD. 5hmC is highly enriched in the nervous system and displays neurodevelopment and age-related changes. To determine the role of 5hmC in AD, we performed genome-wide analyses of 5hmC in DNA from prefrontal cortex of post-mortem AD as well as RNA-Seq to correlate changes in methylation status with transcriptional changes. We also utilized the existing AD fly model to further test the functional significance of these epigenetically altered loci. We identified 325 genes containing differentially hydroxymethylated loci (DhMLs) in both the discovery and replication datasets, and these are enriched for pathways involved in neuron projection development and neurogenesis. Of the 325 genes identified, 140 also showed changes in gene expression by RNA-Seq. Proteins encoded by genes identified in the current analysis form direct protein-protein interactions with AD-associated genes, expanding the network of genes implicated in AD. Furthermore, we identified AD-associated single nucleotide polymorphisms (SNPs) located within or near DhMLs, suggesting that these SNPs may identify regions of epigenetic gene regulation that play a role in AD pathogenesis. Finally using the existing AD fly model we showed that some of these genes could modulate the toxicity associated with AD. Our data implicate neuron projection development and neurogenesis pathways as potential targets in AD. These results indicate that incorporating epigenomic and transcriptomic data with GWAS data can expand the known network of genes involved in disease pathogenesis. Combination of epigenome profiling and Drosophila model enables us to identify the epigenetic modifiers of Alzheimer's disease. University of Kentucky Alzheimer's Disease Research Center (3 control, 3 Alzheimer's) and Emory University Alzheimer's Disease Research Center (2 control, 2 Alzheimer's)

Project description:Kyrtsos2011 - A systems biology model for Alzheimer's disease (Cholesterol in AD) Encoded non-curated model. Issues: - Confusing HmgCoA differential equation - Confusing d2 and t1 parameters - Lack of initial values for several key species This model is described in the article: Of Mice and Math: A Systems Biology Model for Alzheimer's disease Kyrtsos, Christina Rose UMD Theses and Dissertations Abstract: Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder in the US, affecting over 1 in 8 people over the age of 65. There are several well-known pathological changes in the brains of AD patients, namely: the presence of diffuse beta amyloid plaques derived from the amyloid precursor protein (APP), hyper-phosphorylated tau protein, neuroinflammation and mitochondrial dysfunction. Recent studies have shown that cholesterol levels in both the plasma and the brain may play a role in disease pathogenesis, however, this exact role is not well understood. Additional proteins of interest have also been identified (ApoE, LRP-1, IL-1) as possible contributors to AD pathogenesis. To help understand these roles better, a systems biology mathematical model was developed. Basic principles from graph theory and control analysis were used to study the effect of altered cholesterol, ApoE, LRP and APP on the system as a whole. Negative feedback regulation and the rate of cholesterol transfer between astrocytes and neurons were identified as key modulators in the level of beta amyloid. Experiments were run concurrently to test whether decreasing plasma and brain cholesterol levels with simvastatin altered the expression levels of beta amyloid, ApoE, and LRP-1, to ascertain the edge directions in the network model and to better understand whether statin treatment served as a viable treatment option for AD patients. The work completed herein represents the first attempt to create a systems-level mathematical model to study AD that looks at intercellular interactions, as well as interactions between metabolic and inflammatory pathways. This model is hosted on BioModels Database and identified by: MODEL1504240000. To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

Dataset Information

Mizuno2012 - AlzPathway: a comprehensive map of Alzheimer's disease

Publications

AlzPathway: a comprehensive map of signaling pathways of Alzheimer's disease.

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