The interaction of core modules as a basis for elucidating network behavior determining Parkinson's disease pathogenesis

CPT Pharmacometrics & Systems Pharmacology, vol. 13, pp. 335–340

Abstract

In this perspective paper, we show how central aspects of the emergent systems behavior (and malfunctioning) in networks can be understood by systematically studying and examining interactions of key subnetworks as a starting point, demonstrating this in the instance of Parkinson's disease.In so doing, we highlight our systems perspective on analyzing important aspects of network behavior by considering key subnetworks and their interactions.We used focused systems analysis to analyze the interaction of two key subnetworks each containing alpha-synuclein (a core component of the Parkinson's disease network), and reveal the underlying systems landscape of the emergent behavior.This provides non-trivial insights into understanding the origins and key drivers of systems behavior, different ways of targeting nodes for treatment purposes, a basis for stratifying patient populations, and an illuminating platform for more detailed modeling, 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.

Authors 3

1. Govind Menon

   Imperial College London

   Affiliation as printed

   Department of Chemical Engineering, Sargent Centre for Process Systems Engineering Imperial College London London UK

   Department of Chemical Engineering, Sargent Centre for Process Systems Engineering Imperial College London London UK

2. Suruchi Bakshi Aachen Systems Pharmacology and Pharmacy

   Leiden University

   Affiliation as printed

   Certara QSP Breda The Netherlands

   Systems Pharmacology and Pharmacy, LACDR Leiden University Leiden The Netherlands

   Certara QSP Breda The Netherlands

   Systems Pharmacology and Pharmacy, LACDR Leiden University Leiden The Netherlands

3. J. Krishnan corresponding

   Imperial College London

   Affiliation as printed

   Department of Chemical Engineering, Sargent Centre for Process Systems Engineering Imperial College London London UK

   Institute of Systems and Synthetic Biology Imperial College London London UK

   Department of Chemical Engineering, Sargent Centre for Process Systems Engineering Imperial College London London UK

   Institute of Systems and Synthetic Biology Imperial College London London UK