Seed-competent tau monomer initiates pathology in PS19 tauopathy mice
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Orbitrap Fusion Lumos
ORGANISM(S): Homo Sapiens (ncbitaxon:9606)
SUBMITTER: 
Marc I Diamond
PROVIDER: MSV000088651 | MassIVE | Thu Jan 06 11:22:00 GMT 2022
REPOSITORIES: MassIVE
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Project description:Yuraszeck2010 - Vulnerabilities in the Tau
Network in Tau Pathophysiology
This model is described in the article:
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 Comput. Biol. 2010; 6(11):
e1000997
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.
This model is hosted on
BioModels Database
and identified by:
BIOMD0000000542.
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.
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