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WIREs Syst Biol Med
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An energy systems approach to Parkinson's disease

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Abstract The cause of Parkinson's disease (PD) remains unknown despite it being the second most prevalent neurodegenerative condition. Indeed, there is a growing consensus that there is no single cause, and that PD is a multifactorial systemic condition, in which a number of factors may determine its etiopathogenesis. We describe a systems approach that addresses the multifactorial aspects of PD and overcomes constraints on conventional experimentation imposed by PD's causal complexity, its long temporal duration, and its uniqueness to human brains. Specifically, a mathematical model of brain energy metabolism is used as a core module to which other modules describing cellular processes thought to be associated with PD can be attached and studied in an integrative environment. Employing brain energy usage as the core of a systems approach also enables the potential role that compromised energy metabolism may have in the etiology of PD. Although developed for PD, it has not escaped our attention that the energy systems approach outlined here could also be applied to other neurodegenerative disorders—most notably Alzheimer's disease. WIREs Syst Biol Med 2011 3 1–6 DOI: 10.1002/wsbm.107 This article is categorized under: Analytical and Computational Methods > Computational Methods Analytical and Computational Methods > Dynamical Methods Biological Mechanisms > Metabolism

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A multifactorial view of Parkinson's disease, with potential etiological categories: (a) Inherited features, (b) age and lifetime experiences, and (c) neurochemical processes associated with PD pathology.

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Illustrating the impact of transient energy demands on compromised brain energy metabolism efficiency. Increases in energy demand associated with neural stimulation cause temporary dips in available ATP. The dips quickly become significant even for moderately compromised energy metabolism.

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Illustrating the impact of age‐ and lifestyle‐related decrease in brain energy metabolism efficiency on steady‐state homeostasis. The impact of gradual decline is held back by robust steady‐state homeostatic control until the decline is overwhelming and ATP regulation collapses.

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Schema of the brain energy metabolism model, illustrating the principal exchanges between the compartments (Reprinted with permission. Copyright 2010 IEEE).

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The brain energy metabolism as an interconnective framework, in which ATP links energy sources (glucose and oxygen) with energy‐consuming cellular processes (Reprinted with permission. Copyright 2010 IEEE).

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Biological Mechanisms > Metabolism
Analytical and Computational Methods > Computational Methods
Analytical and Computational Methods > Dynamical Methods

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