BLENX MODELS OF α-SYNUCLEIN AND PARKIN KINETICS IN NEUROPATHOLOGY OF PARKINSON'S DISEASE

Abstract

In this paper two stochastic kinetic models of a faulty ubiquitin–proteasome are presented. In the first model, mutant variants of the α-synuclein, induced by environmental stress factors, inhibit the ubiquitin–proteasome pathway that is in charge to start the degradation of misfolded proteins. In the second model mutant variants of parkin proteins are not able to transfer the ubiquitin molecules on the faulty proteins, so that they are not targeted and recognized as toxic products. The models are specified in BlenX and simulated with Beta Workbench (Beta WB) simulator. BlenX is a new programming language that has been recently designed by the CoSBi team of researchers to describe components and interactions among components of a biochemical system. It implements a process calculus in which the communication and synchronization between computational processes abstract the biochemical interaction and reactions between molecules, proteins and functional complexes. The aim of this study is twofold: (i) to move the current focus on the structural studies of the components of the protein ubiquitination and degradation to the dynamics of such components in a typical systems biology perspective; (ii) to provide first stochastic models in a new language suitable to systemic approach to the modelling of biochemical kinetics. This tool makes it possible for biologists and medical researchers a high-level modeling of molecular mechanisms underlying the pathogenesis of the disease. Consequently, the suitable abstraction provided by the language makes possible the elucidation of important and still elusive aspects of the involved biochemical interactions. The agreement of the simulations of our models with the available qualitative experimental observations and previous theoretical studies supports the confidence in the model validity.