Paper Info
Title
Vulnerabilities in the Tau Network and the Role of Ultrasensitive Points in Tau Pathophysiology.
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.
Year
DOI
Venue
2010
10.1371/journal.pcbi.1000997
PLOS COMPUTATIONAL BIOLOGY
Field
DocType
Volume
Population,Biology,Alzheimer's disease,Identifiability,Systems biology,Bioinformatics,Brain chemistry,In silico
Journal
6
Issue
Citations 
PageRank 
11
1
0.36
References 
Authors
2
6
Name
Order
Citations
PageRank
Theresa M. Yuraszeck110.36
Pierre Neveu210.36
Maria Rodriguez-Fernandez316211.05
Anne Robinson410.36
Kenneth S. Kosik561.50
Francis J. Doyle III6889.23