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.
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Audald Lloret i Villas 
