دورية أكاديمية
Vulnerabilities in the tau network and the role of ultrasensitive points in tau pathophysiology.
| العنوان: | Vulnerabilities in the tau network and the role of ultrasensitive points in tau pathophysiology. |
|---|---|
| المؤلفون: | Theresa M Yuraszeck, Pierre Neveu, Maria Rodriguez-Fernandez, Anne Robinson, Kenneth S Kosik, Francis J Doyle |
| المصدر: | PLoS Computational Biology, Vol 6, Iss 11, p e1000997 (2010) |
| بيانات النشر: | Public Library of Science (PLoS), 2010. |
| سنة النشر: | 2010 |
| المجموعة: | LCC:Biology (General) |
| مصطلحات موضوعية: | Biology (General), QH301-705.5 |
| الوصف: | 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. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1553-734X 1553-7358 |
| العلاقة: | http://europepmc.org/articles/PMC2978700?pdf=renderTest; https://doaj.org/toc/1553-734XTest; https://doaj.org/toc/1553-7358Test |
| DOI: | 10.1371/journal.pcbi.1000997 |
| الوصول الحر: | https://doaj.org/article/99a8da51ecab4091a0cf5aec9f6e3ee9Test |
| رقم الانضمام: | edsdoj.99a8da51ecab4091a0cf5aec9f6e3ee9 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 1553734X 15537358 |
|---|---|
| DOI: | 10.1371/journal.pcbi.1000997 |