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Poliquin2013 - Energy Deregulations in Parkinson's Disease


ABSTRACT: Poliquin2013 - Energy Deregulations in Parkinson's Disease Encoded non-curated model. Issues: - Fluxes, reactions, parameters and species properly encoded but Figure 2 not successfully simulated. - Unpaired values in Table 5 and Matlab Code (S5 and S6 Supplementary Material): Vm_ldh_r, Vm_t_lac, Km_ldh_nadh, Vm_cdh, Vm_cd, Vm_fh, Cm_ldh_f,Vm_sdh and Vm_pdh - Confusing parameter t2 on unitpulseSB; is it T_p_off or (T_p_off + T_p_on)? This model is described in the article: Metabolomics and in-silico analysis reveal critical energy deregulations in animal models of Parkinson's disease. Poliquin PO, Chen J, Cloutier M, Trudeau LÉ, Jolicoeur M. PLoS ONE 2013; 8(7): e69146 Abstract: Parkinson's disease (PD) is a multifactorial disease known to result from a variety of factors. Although age is the principal risk factor, other etiological mechanisms have been identified, including gene mutations and exposure to toxins. Deregulation of energy metabolism, mostly through the loss of complex I efficiency, is involved in disease progression in both the genetic and sporadic forms of the disease. In this study, we investigated energy deregulation in the cerebral tissue of animal models (genetic and toxin induced) of PD using an approach that combines metabolomics and mathematical modelling. In a first step, quantitative measurements of energy-related metabolites in mouse brain slices revealed most affected pathways. A genetic model of PD, the Park2 knockout, was compared to the effect of CCCP, a complex I blocker. Model simulated and experimental results revealed a significant and sustained decrease in ATP after CCCP exposure, but not in the genetic mice model. In support to data analysis, a mathematical model of the relevant metabolic pathways was developed and calibrated onto experimental data. In this work, we show that a short-term stress response in nucleotide scavenging is most probably induced by the toxin exposure. In turn, the robustness of energy-related pathways in the model explains how genetic perturbations, at least in young animals, are not sufficient to induce significant changes at the metabolite level. This model is hosted on BioModels Database and identified by: MODEL1410060000. To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

DISEASE(S): Parkinson's Disease

SUBMITTER: Audald Lloret i Villas  

PROVIDER: MODEL1410060000 | BioModels | 2015-02-25

REPOSITORIES: BioModels

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Publications

Metabolomics and in-silico analysis reveal critical energy deregulations in animal models of Parkinson's disease.

Poliquin Pierre O PO   Chen Jingkui J   Cloutier Mathieu M   Trudeau Louis-Éric LÉ   Jolicoeur Mario M  

PloS one 20130723 7


Parkinson's disease (PD) is a multifactorial disease known to result from a variety of factors. Although age is the principal risk factor, other etiological mechanisms have been identified, including gene mutations and exposure to toxins. Deregulation of energy metabolism, mostly through the loss of complex I efficiency, is involved in disease progression in both the genetic and sporadic forms of the disease. In this study, we investigated energy deregulation in the cerebral tissue of animal mod  ...[more]

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