A pragmatic approach to biochemical systems theory applied to an α-synuclein-based model of Parkinson's disease

Neurodegenerative diseases are a heterogeneous group of disorders that are characterized by the progressive dysfunction and loss of neurons. Here, we distil and discuss the current state of modeling in the area of neurodegeneration, and objectively compare the gaps between existing clinical knowledge and the mechanistic understanding of the major pathological processes implicated in neurodegenerative disorders. We also discuss new directions in the field of neurodegeneration that hold potential for furthering therapeutic interventions and strategies.

show abstract

“…Several computational models have been formulated to study the role of DA metabolism in α‐Syn aggregation 19, 24, 57, 58, 59.…”

Section: Resultsmentioning

confidence: 99%

“…Parkin, synphilin and ubiquitin (Ub) are essential components of the Lewy Bodies and are studied in an integrative model by Sass et al (2009) 59.…”

Section: Resultsmentioning

confidence: 99%

The Impact of Mathematical Modeling in Understanding the Mechanisms Underlying Neurodegeneration: Evolving Dimensions and Future Directions

Lloret-Villas

Varusai

Juty

et al. 2017

CPT Pharmacom & Syst Pharma

View full text Add to dashboard Cite

show abstract

“…The mathematical principles behind the computational framework are discussed but not resolved in great detail. For further review of this particular methodology, see Sass et al (2009), and for a comprehensive description on biochemical systems theory (BST), see Savageau (1969aSavageau ( ,b, 1970 and Voit (2000). Due to complexity of this system, not every relationship or characterization will be explained, so a visual diagram and the mathematical framework for the entire system may be found in the supporting information (Supplementary Figs.…”

Section: Methodsmentioning

confidence: 99%

“…We recently reported our first stage of model development, which addressed fundamental components in PD pathology: ␣-synuclein aggregation, dopamine metabolism, lysosomal degradation, and the ubiquitin-proteasome system (Sass et al, 2009). In an effort to generate a more refined and comprehensive model of PD, the focus of this study resolved to copper, iron, and dopamine metabolism in SNpc neurons.…”

Section: Introductionmentioning

confidence: 99%

In silico evidence for glutathione- and iron-related pathogeneses in Parkinson's disease

Yeager

Coleman

2010

Journal of Neuroscience Methods

Self Cite

View full text Add to dashboard Cite

“…e work of Qi's group contains models for the presynapse, which is a nerve ending in the midbrain where dopamine is produced, as well as the postsynapse in the forebrain, where dopamine signals are interpreted. Sass and colleagues used a complementary BST model to investigate the dynamics of the protein -synuclein, which is the second hallmark of Parkinson's disease, outside changes in dopamine levels [613].…”

Section: Human Physiology and Diseasementioning

confidence: 99%

Biochemical Systems Theory: A Review

Voit

2013

ISRN Biomathematics

149

154

View full text Add to dashboard Cite

Biochemical systems theory (BST) is the foundation for a set of analytical andmodeling tools that facilitate the analysis of dynamic biological systems. is paper depicts major developments in BST up to the current state of the art in 2012. It discusses its rationale, describes the typical strategies and methods of designing, diagnosing, analyzing, and utilizing BST models, and reviews areas of application. e paper is intended as a guide for investigators entering the fascinating �eld of biological systems analysis and as a resource for practitioners and experts. PreambleBiochemical systems theory (BST) is a mathematical and computational framework for analyzing and simulating systems. It was originally developed for biochemical pathways but by now has become much more widely applied to systems throughout biology and beyond. BST is called "canonical, " which means that model construction, diagnosis, and analysis follow stringent rules, which will be discussed throughout this paper. e key ingredient of BST is the power-law representation of all processes in a system.BST has been the focus of a number of books [1-6], including some in Chinese and Japanese [7][8][9]. e most detailed modern text dedicated speci�cally to BST is [3]. Moreover, since its inception, numerous reviews have portrayed the evolving state of the art in BST. Most of these reviews summarized methodological advances for the analysis of biochemical pathway systems . Others compared BST models with alternative modeling frameworks [32,[51][52][53][54][55][56][57][58][59][60][61][62][63]; some of these comparisons will be discussed later. Yet other reviews focused on specialty areas, such as customized methods for optimizing BST models (e.g., [64][65][66][67]) or estimating their parameters (e.g., [68][69][70][71][72]), strategies for discovering design and operating principles in natural system (e.g., [73][74][75][76][77][78]), and even the use of BST models in statistics [79][80][81]. A historical account of the �rst twenty years of BST was presented in [82].Supporting the methodological developments in the �eld, several soware packages were developed for different aspects of BST analysis. e earliest was ESSYNS [83][84][85], which supported all standard steady-state analyses and also contained a numerical solver that, at the time, was many times faster than any off-the-shelf soware [86,87]; see also [88]. Utilizing advances in computing and an extension of the solver from ESSYNS, Ferreira created the very user-friendly package PLAS, which is openly available and still very widely used [89] (see also [3]). Yamada and colleagues developed soware to translate E-cell models into BST models in PLAS format [90]. Okamoto's group created the soware BestKit, which permits the graphical design and translation of models, along with their analysis [91][92][93]. Vera and colleagues developed the soware tool PLMaddon for analyzing BST models within SBML [94]; see also [95]. It expands the Matlab SBToolbox with speci�c functionalities for power-law repr...

show abstract

A pragmatic approach to biochemical systems theory applied to an α-synuclein-based model of Parkinson's disease

Cited by 14 publications

References 90 publications

The Impact of Mathematical Modeling in Understanding the Mechanisms Underlying Neurodegeneration: Evolving Dimensions and Future Directions

The Impact of Mathematical Modeling in Understanding the Mechanisms Underlying Neurodegeneration: Evolving Dimensions and Future Directions

In silico evidence for glutathione- and iron-related pathogeneses in Parkinson's disease

Biochemical Systems Theory: A Review

Contact Info

Product

Resources

About