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Network analysis reveals strain-dependent response to misfolded tau aggregates

ABSTRACT: To investigate the effect of wild-derived genetic background on modeling tau aggregation, we injected either AAV-eGFP or AAV-hTauP301L into postnatal day 0 mice to drive widespread expression. We then performed gene expression profiling analysis using data obtained from mRNA-seq from mouse brain cortex of 6 month old hTauP301L- or eGFP-mice.

ORGANISM(S): Mus musculus

PROVIDER: GSE223840 | GEO | 2023/07/25

REPOSITORIES: GEO

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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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Network analysis reveals strain-dependent response to misfolded tau aggregates

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