A mathematical model of insulin resistance in Parkinson's disease. (June 2015)

• Record Type: Journal Article
• Authors: Braatz, Elise M.; Coleman, Randolph A.
• Is Part Of: Computational biology and chemistry. Volume 56(2015)
• Page Start: 84
• Page End: 97
• Publication Date: 2015-06
• Subjects: BST biochemical systems theory -- PLAS power law analysis and simulation -- PD Parkinson's disease -- T2DM type-II diabetes mellitus -- ROS reactive oxygen species -- RNS reactive nitrogen species -- ODE ordinary differential equation -- PPARG peroxisome-proliferator-activated receptor γ -- IL-6 interleukin-6 -- IL-1β interleukin-1β -- TNFα tumor necrosis factor α -- MCSF macrophage colony-stimulating factor -- COX2 cyclooxygenase 2 -- NO nitric oxide -- H2O2 hydrogen peroxide -- O2- superoxide radical -- OH- hydroxyl radical -- ONOO- peroxynitrite -- HNO2 nitrous acid -- NF-κB nuclear factor κB -- VMAT vesicular monoamine transporter proteins -- SOD2 superoxide dismutase 2 -- PI3K phosphatidylinositol 3 kinase -- PIP2 phosphatidylinositol bisphosphate -- PIP3 phosphatidylinositol trisphosphate -- GSK-3β glycogen synthase kinase 3β -- MKP-1 mitogen-activated protein kinase phosphatase 1 -- DUPS1 dual specificity protein phosphatase 1 -- PTP permeability transition pore -- AIF apoptosis-inducing factor -- SMAC/DIABLO second mitochondria-derived activator of caspases/direct iap binding protein with low pI -- IAP inhibitor of apoptosis -- NAC N-acetylcysteine -- NOS nitric oxide synthase -- NSAID non-steroidal anti-inflammatory drug -- ALS amyotrophic lateral sclerosis; Parkinson's disease -- Insulin resistance -- Computational biology -- Neurodegenerative disease -- Type-II diabetes mellitus -- Delayed treatment; Chemistry -- Data processing -- Periodicals; Biology -- Data processing -- Periodicals; Biochemistry -- Data processing; Biology -- Data processing; Molecular biology -- Data processing; Periodicals; Electronic journals; 542.85
• DOI: 10.1016/j.compbiolchem.2015.04.003
• Languages: English
• ISSNs: 1476-9271

Abstract

Graphical abstract: Highlights: Inflammation and oxidative stress cause insulin resistance in Parkinson's disease. Parkinson's disease is accentuated by insulin resistance. A combination of treatment options proves effective against Parkinson's disease. Delayed treatment states provide a more realistic view of drug efficacy. Abstract: This paper introduces a mathematical model representing the biochemical interactions between insulin signaling and Parkinson's disease. The model can be used to examine the changes that occur over the course of the disease as well as identify which processes would be the most effective targets for treatment. The model is mathematized using biochemical systems theory (BST). It incorporates a treatment strategy that includes several experimental drugs along with current treatments. In the past, BST models of neurodegeneration have used power law analysis and simulation (PLAS) to model the system. This paper recommends the use of MATLAB instead. MATLAB allows for more flexibility in both the model itself and in data analysis. Previous BST analyses of neurodegeneration began treatment at disease onset. As shown in this model, the outcomes of delayed, realistic treatment and full treatment at disease onset are significantly different. The delayed treatment strategy is an important development in BST modeling of neurodegeneration. It emphasizes the importance of early diagnosis, and allows for a more accurate representation of disease and treatment interactions.