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A systems approach to Parkinson ’ s disease

We describe a systems approach to Parkinson’s disease in which an integrative mathematical model of the brain energy metabolism is used as the basis for in–silico investigation of possible disease mechanisms. The mathematical model allows both the analysis of dynamical and structural implications of biological factors implicated in disease causation, and the potential role of a compromised brain energy metabolism as factor that enables pathologies associated with the disease to develop. Using a recently developed mathematical model of brain energy metabolism, we use simulations of brain energy behaviour to illustrate how a weakened energy metabolism might create a cellular environment where pathogenic mechanisms that are normally held in check by an efficient energy metabolism could potentially flourish. Simulations of the brain energy metabolism are presented which illustrate how both very long term deterioration of metabolism, and cumulative stress from energy transients, may create a predisposition to Parkinson’s disease. The focus of this study is Parkinson’s disease, but we note that our energy metabolism modelling and analysis framework may also form a basis for a systems approach to other age–related neurodegenerative conditions. ∗The Hamilton Institute National University of Ireland Maynooth, County Kildare, Ireland.