Biology – Quantitative Biology – Quantitative Methods
Scientific paper
2011-07-14
Biology
Quantitative Biology
Quantitative Methods
Scientific paper
To study the kinetic effects of possible coupling between the cellular, surface bound PrPC protein and the A{\beta} peptide of Alzheimer's disease, we introduce and simulate a model that includes A{\beta} aggregation in the extra-cellular environment and on the cell-surface assisted by a PrPC. The model also includes supply, clearance, production and sequestration of free and membrane bound peptides, proteins and aggregates. The model is used to produce homeostatic phase diagrams for the onset of aggregation and of reduced stable A{\beta} monomer concentration due to aggregation; the resultant phase boundaries depend nontrivially upon concentrations and reaction rate parameters. We identify ranges of parameter values which give monomer concentration depletion upon aggregation similar to that observed in humans. We show that inferences about the lack of PrPC - A{\beta} coupling may be incorrect due to the influence of large A{\beta} concentration from overexpression. The magnitude of the PrPc effect on aggregation depends on initial state and reaction parameters.
Cox Daniel
Dar Youval
Singh Rajiv
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