In this perspective paper we show how central aspects of the emergent systems network behaviour (and malfunctioning) can be understood by systematically studying and examining interactions of key sub-networks
as a starting point, demonstrating this in the instance of Parkinson’s disease.In so doing, we highlight our systems perspective on how important aspects of network behaviour can be revealed by considering the interactions of key subnetworks. Parkinson’s disease is a multi-factorial disease, influenced by a number of internal and external factors, where therapeutic approaches have had limited success. Understanding the functioning of the underlying network is a key aspect of elucidating pathogenesis. We focus on two key sub-networks, each containing alpha-synuclein (alphasyn) (a core component of the Parkinson’s disease network). Each of these sub-networks is characterized by strong non-linearity and feedback effects. We employ focused systems analysis to analyze the interaction of these sub-networks and reveal the underlying systems landscape of the emergent behaviour.This provides non-trivial insights into understanding the origins and key drivers of systems behaviour, different ways of targeting nodes for treatment purposes, a basis for stratifying patient populations and an illuminating platform for more detailed modelling, which it can be used in conjunction with. We also demonstrate how the basic framework can be built upon to examine the effect of dopamine compartmentalization.
This approach represents a distinct way of dissecting nonlinear networks and can be adapted and used in other disease contexts as well.