Yuraszeck2010 - Vulnerabilities in the Tau Network in Tau Pathophysiology
This model is described in the article:
Abstract:
The multifactorial nature of disease motivates the use of systems-level analyses to understand their pathology. We used a systems biology approach to study tau aggregation, one of the hallmark features of Alzheimer's disease. A mathematical model was constructed to capture the current state of knowledge concerning tau's behavior and interactions in cells. The model was implemented in silico in the form of ordinary differential equations. The identifiability of the model was assessed and parameters were estimated to generate two cellular states: a population of solutions that corresponds to normal tau homeostasis and a population of solutions that displays aggregation-prone behavior. The model of normal tau homeostasis was robust to perturbations, and disturbances in multiple processes were required to achieve an aggregation-prone state. The aggregation-prone state was ultrasensitive to perturbations in diverse subsets of networks. Tau aggregation requires that multiple cellular parameters are set coordinately to a set of values that drive pathological assembly of tau. This model provides a foundation on which to build and increase our understanding of the series of events that lead to tau aggregation and may ultimately be used to identify critical intervention points that can direct the cell away from tau aggregation to aid in the treatment of tau-mediated (or related) aggregation diseases including Alzheimer's.
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Vulnerabilities in the tau network and the role of ultrasensitive points in tau pathophysiology.
- Yuraszeck TM, Neveu P, Rodriguez-Fernandez M, Robinson A, Kosik KS, Doyle FJ 3rd
- PLoS computational biology , 11/ 2010 , Volume 6 , pages: e1000997
- Department of Chemical Engineering, University of California, Santa Barbara, Santa Barbara, California, USA.
- The multifactorial nature of disease motivates the use of systems-level analyses to understand their pathology. We used a systems biology approach to study tau aggregation, one of the hallmark features of Alzheimer's disease. A mathematical model was constructed to capture the current state of knowledge concerning tau's behavior and interactions in cells. The model was implemented in silico in the form of ordinary differential equations. The identifiability of the model was assessed and parameters were estimated to generate two cellular states: a population of solutions that corresponds to normal tau homeostasis and a population of solutions that displays aggregation-prone behavior. The model of normal tau homeostasis was robust to perturbations, and disturbances in multiple processes were required to achieve an aggregation-prone state. The aggregation-prone state was ultrasensitive to perturbations in diverse subsets of networks. Tau aggregation requires that multiple cellular parameters are set coordinately to a set of values that drive pathological assembly of tau. This model provides a foundation on which to build and increase our understanding of the series of events that lead to tau aggregation and may ultimately be used to identify critical intervention points that can direct the cell away from tau aggregation to aid in the treatment of tau-mediated (or related) aggregation diseases including Alzheimer's.
Metadata information
| Name | Description | Size | Actions |
|---|---|---|---|
Model files |
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| BIOMD0000000542_url.xml | SBML L2V4 representation of Yuraszeck2010 - Vulnerabilities in the Tau Network in Tau Pathophysiology | 298.36 KB | Preview | Download |
Additional files |
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| BIOMD0000000542.png | Auto-generated Reaction graph (PNG) | 3.83 MB | Preview | Download |
| BIOMD0000000542.xpp | Auto-generated XPP file | 21.04 KB | Preview | Download |
| BIOMD0000000542.pdf | Auto-generated PDF file | 604.47 KB | Preview | Download |
| BIOMD0000000542.svg | Auto-generated Reaction graph (SVG) | 289.39 KB | Preview | Download |
| BIOMD0000000542_urn.xml | Auto-generated SBML file with URNs | 296.58 KB | Preview | Download |
| 5Yuraszeck2010.cps | Copasi file of “Tau04MT” concentration when 5-fold increase in reaction 12 is implemented | 330.58 KB | Preview | Download |
| BIOMD0000000542.m | Auto-generated Octave file | 27.52 KB | Preview | Download |
| BIOMD0000000542-biopax2.owl | Auto-generated BioPAX (Level 2) | 131.31 KB | Preview | Download |
| BIOMD0000000542.sci | Auto-generated Scilab file | 154.00 bytes | Preview | Download |
| Yuraszeck2010.cps | Copasi file of “Tau04MT” basal concentration | 332.64 KB | Preview | Download |
| BIOMD0000000542-biopax3.owl | Auto-generated BioPAX (Level 3) | 228.77 KB | Preview | Download |
| BIOMD0000000542.vcml | Auto-generated VCML file | 900.00 bytes | Preview | Download |
- Model originally submitted by : Audald Lloret i Villas
- Submitted: Aug 15, 2014 10:58:21 AM
- Last Modified: Dec 21, 2018 5:33:06 PM
Revisions
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Version: 3
- Submitted on: Dec 21, 2018 5:33:06 PM
- Submitted by: administrator
- With comment: Include the additional files provided by the submitter in the original submission: Yuraszeck2010.cps, 5Yuraszeck2010.cps
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Version: 2
- Submitted on: Sep 23, 2014 7:41:53 PM
- Submitted by: Audald Lloret i Villas
- With comment: Current version of Yuraszeck2010 - Vulnerabilities in the Tau Network in Tau Pathophysiology
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Version: 1
- Submitted on: Aug 15, 2014 10:58:21 AM
- Submitted by: Audald Lloret i Villas
- With comment: Original import of Yuraszeck2010 - Vulnerabilities in the Tau Network in Tau Pathophysiology
(added: 15 Aug 2014, 12:18:53, updated: 15 Aug 2014, 12:18:53)