A constraint-based modelling approach to metabolic dysfunction in Parkinson's disease

One of the hallmarks of sporadic Parkinson's disease is degeneration of dopaminergic neurons in the pars compacta of the substantia nigra. The aetiopathogenesis of this degeneration is still not fully understood, with dysfunction of many biochemical pathways in different subsystems suggested to be involved. Recent advances in constraint-based modelling approaches hold great potential to systematically examine the relative contribution of dysfunction in disparate pathways to dopaminergic neuronal degeneration, but few studies have employed these methods in Parkinson's disease research. Therefore, this review outlines a framework for future constraint-based modelling of dopaminergic neuronal metabolism to decipher the multi-factorial mechanisms underlying the neuronal pathology of Parkinson's disease.