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
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Figure 2 and 3 of this article originally appeared in ‘Systems Biology and the Spirit of Tustin’, February 2010, IEEE Control Systems Magazine. The curated forms of the energy metabolism model (Figure 3) used here24 and the generic models of energy metabolism systems structures23 are lodged the CellML repository (http://models.cellml.org) in the category—metabolism.