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Modeling Protein and Oxidative Metabolism in Parkinson’s Disease

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Systems Biology of Parkinson's Disease

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Abstract

Elevated levels of reactive oxygen species (ROS) and accumulation of misfolded α-synuclein (αSYN) are recurrent features in a majority of Parkinson’s disease cases. Building on the brain energy metabolism framework in Chap. 2, a mathematical model is constructed of these key neurochemical players and their interactions. A computer implementation of the model is used to simulate and visualize the dynamics of ROS, αSYN, and their nonlinear interaction within a positive feedback loop. The most important observation from this modeling is that the homogenous nature of known biomarkers (ROS/αSYN) can be reconciled with the heterogeneous nature of the underlying risk factors, including aging, genetics, and toxins. More specifically, our model uses risk factors (aging, toxins) as “inputs” and then provides estimates of PD susceptibility based on their propensity to destabilize the model system. The stability of the model is then used as a criterion to quantify the level of various risks. The importance of rapid biochemical dynamics in evaluating the impact of neuroprotective strategies is also highlighted, with simulations demonstrating the synergistic effect of creatine and antioxidants in buffering ROS levels during transient conditions.

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Author information

Authors and Affiliations

  1. GERAD, Ecole Polytechnique de Montreal, Montreal, QC, Canada

    Mathieu Cloutier

  2. Hamilton Institute, National University of Ireland, Maynooth, County Kildare, Ireland

    Peter Wellstead

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  1. Mathieu Cloutier
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  2. Peter Wellstead
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Correspondence to Mathieu Cloutier .

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Editors and Affiliations

  1. , Hamilton Institute, National University of Ireland, Maynooth, Maynooth, Kildare, Ireland

    Peter Wellstead

  2. Ecole Polytechnique de Montreal, C.P. 6079, Succ. Centre-ville, Montreal, H3C 3A7, Québec, Canada

    Mathieu Cloutier

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Cloutier, M., Wellstead, P. (2012). Modeling Protein and Oxidative Metabolism in Parkinson’s Disease. In: Wellstead, P., Cloutier, M. (eds) Systems Biology of Parkinson's Disease. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-3411-5_7

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