Computational Modelling of TNFalpha Pathway in Parkinson's Disease (Sasidharakurup et al 2019)

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Accession:263585
"The paper aims developing a computational framework of signaling using the principles of biochemical systems theory as a model for Parkinson’s disease. Several molecular interactions aided by TNFalpha, a proinflammatory cytokine play key roles in mediating glutamate excitotoxicity and neuroinflammation, resulting in neuronal cell death. In this paper, initial concentrations and rate constants were extracted from literature and simulations developed were based on systems of ordinary differential equations following first-order kinetics. In control or healthy conditions, a decrease in TNFalpha and neuronal cell death was predicted in simulations matching data from experiments, whereas in diseased condition, a drastic increase in levels of TNFalpha, glutamate, TNFR1 and ROS were observed similar to experimental data correlating diseased condition to augmented neuronal cell death. The study suggests toxic effects induced by TNFalpha in the substantia nigra may be attributed to Parkinson’s disease conditions."
Reference:
1 . Sasidharakurup H, Nair L, Bhaskar K, Diwakar S (2020) Computational Modelling of TNFa Pathway in Parkinson’s Disease – A Systemic Perspective Complex Networks and Their Applications VIII. COMPLEX NETWORKS 2019. Studies in Computational Intell, Cherifi H, Gaito S, Mendes J, Moro E, Rocha L, ed.
Model Information (Click on a link to find other models with that property)
Model Type:
Brain Region(s)/Organism:
Cell Type(s):
Channel(s):
Gap Junctions:
Receptor(s):
Gene(s):
Transmitter(s): Glutamate;
Simulation Environment: CellDesigner;
Model Concept(s): Parkinson's; Signaling pathways;
Implementer(s): Diwakar, Shyam [shyam at amrita.edu];
Search NeuronDB for information about:  Glutamate;
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Sasidharakurp2019
README.txt
Exocitotoxicity.xml
Inflammation.xml
                            
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<speciesReference metaid="CDMT00079" species="s29"/>
</listOfProducts>
<kineticLaw metaid="CDMT00080">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<times/>
<ci> s20 </ci>
<ci> k1 </ci>
</apply>
</math>
<listOfParameters>
<parameter metaid="CDMT00081" id="k1" name="k1" value="0.1" units="substance"/>
</listOfParameters>
</kineticLaw>
</reaction>
<reaction metaid="re39" id="re39" reversible="false" fast="false">
<annotation/>
<listOfReactants>
<speciesReference metaid="CDMT00082" species="s54"/>
</listOfReactants>
<listOfProducts>
<speciesReference metaid="CDMT00083" species="s56"/>
</listOfProducts>
<kineticLaw metaid="CDMT00084">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<times/>
<ci> s54 </ci>
<ci> k1 </ci>
</apply>
</math>
<listOfParameters>
<parameter metaid="CDMT00085" id="k1" name="k1" value="0.1" units="substance"/>
</listOfParameters>
</kineticLaw>
</reaction>
<reaction metaid="re40" id="re40" reversible="false" fast="false">
<annotation/>
<listOfReactants>
<speciesReference metaid="CDMT00086" species="s56"/>
<speciesReference metaid="CDMT00087" species="s59"/>
<speciesReference metaid="CDMT00088" species="s58"/>
</listOfReactants>
<listOfProducts>
<speciesReference metaid="CDMT00089" species="s57"/>
</listOfProducts>
<kineticLaw metaid="CDMT00090">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<times/>
<ci> s56 </ci>
<ci> s59 </ci>
<ci> s58 </ci>
<ci> k1 </ci>
</apply>
</math>
<listOfParameters>
<parameter metaid="CDMT00091" id="k1" name="k1" value="0.1" units="substance"/>
</listOfParameters>
</kineticLaw>
</reaction>
<reaction metaid="re41" id="re41" reversible="false" fast="false">
<annotation/>
<listOfReactants>
<speciesReference metaid="CDMT00092" species="s57"/>
</listOfReactants>
<listOfProducts>
<speciesReference metaid="CDMT00093" species="s20"/>
</listOfProducts>
<kineticLaw metaid="CDMT00094">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<times/>
<ci> s57 </ci>
<ci> k1 </ci>
</apply>
</math>
<listOfParameters>
<parameter metaid="CDMT00095" id="k1" name="k1" value="0.001" units="substance"/>
</listOfParameters>
</kineticLaw>
</reaction>
<reaction metaid="re42" id="re42" reversible="false" fast="false">
<annotation/>
<listOfReactants>
<speciesReference metaid="CDMT00096" species="s20"/>
</listOfReactants>
<listOfProducts>
<speciesReference metaid="CDMT00097" species="s53"/>
</listOfProducts>
<kineticLaw metaid="CDMT00098">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<times/>
<ci> s20 </ci>
<ci> k1 </ci>
</apply>
</math>
<listOfParameters>
<parameter metaid="CDMT00099" id="k1" name="k1" value="0.01" units="substance"/>
</listOfParameters>
</kineticLaw>
</reaction>
<reaction metaid="re43" id="re43" reversible="false" fast="false">
<annotation/>
<listOfReactants>
<speciesReference metaid="CDMT00100" species="s53"/>
<speciesReference metaid="CDMT00101" species="s62"/>
</listOfReactants>
<listOfProducts>
<speciesReference metaid="CDMT00102" species="s60"/>
</listOfProducts>
<kineticLaw metaid="CDMT00103">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<times/>
<ci> s53 </ci>
<ci> s62 </ci>
<ci> k1 </ci>
</apply>
</math>
<listOfParameters>
<parameter metaid="CDMT00104" id="k1" name="k1" value="0.1" units="substance"/>
</listOfParameters>
</kineticLaw>
</reaction>
<reaction metaid="re46" id="re46" reversible="false" fast="false">
<annotation/>
<listOfReactants>
<speciesReference metaid="CDMT00105" species="s60"/>
</listOfReactants>
<listOfProducts>
<speciesReference metaid="CDMT00106" species="s61"/>
</listOfProducts>
<kineticLaw metaid="CDMT00107">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<times/>
<ci> s60 </ci>
<ci> k1 </ci>
</apply>
</math>
<listOfParameters>
<parameter metaid="CDMT00108" id="k1" name="k1" value="0.1" units="substance"/>
</listOfParameters>
</kineticLaw>
</reaction>
<reaction metaid="re48" id="re48" reversible="false" fast="false">
<annotation/>
<listOfReactants>
<speciesReference metaid="CDMT00109" species="s61"/>
</listOfReactants>
<listOfProducts>
<speciesReference metaid="CDMT00110" species="s63"/>
</listOfProducts>
<kineticLaw metaid="CDMT00111">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<times/>
<ci> s61 </ci>
<ci> k1 </ci>
</apply>
</math>
<listOfParameters>
<parameter metaid="CDMT00112" id="k1" name="k1" value="0.1" units="substance"/>
</listOfParameters>
</kineticLaw>
</reaction>
<reaction metaid="re49" id="re49" reversible="false" fast="false">
<annotation/>
<listOfReactants>
<speciesReference metaid="CDMT00113" species="s63"/>
</listOfReactants>
<listOfProducts>
<speciesReference metaid="CDMT00114" species="s46"/>
</listOfProducts>
<kineticLaw metaid="CDMT00115">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<times/>
<ci> s63 </ci>
<ci> k1 </ci>
</apply>
</math>
<listOfParameters>
<parameter metaid="CDMT00116" id="k1" name="k1" value="0.01" units="substance"/>
</listOfParameters>
</kineticLaw>
</reaction>
<reaction metaid="re50" id="re50" reversible="false" fast="false">
<annotation/>
<listOfReactants>
<speciesReference metaid="CDMT00117" species="s69"/>
</listOfReactants>
<listOfProducts>
<speciesReference metaid="CDMT00118" species="s68"/>
</listOfProducts>
<listOfModifiers>
<modifierSpeciesReference metaid="CDMT00119" species="s71"/>
</listOfModifiers>
<kineticLaw metaid="CDMT00120">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<times/>
<ci> s69 </ci>
<ci> k1 </ci>
</apply>
</math>
<listOfParameters>
<parameter metaid="CDMT00121" id="k1" name="k1" value="0.1" units="substance"/>
</listOfParameters>
</kineticLaw>
</reaction>
<reaction metaid="re51" id="re51" reversible="false" fast="false">
<annotation/>
<listOfReactants>
<speciesReference metaid="CDMT00122" species="s20"/>
</listOfReactants>
<listOfProducts>
<speciesReference metaid="CDMT00123" species="s71"/>
</listOfProducts>
<kineticLaw metaid="CDMT00124">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<times/>
<ci> s20 </ci>
<ci> k1 </ci>
</apply>
</math>
<listOfParameters>
<parameter metaid="CDMT00125" id="k1" name="k1" value="0.1" units="substance"/>
</listOfParameters>
</kineticLaw>
</reaction>
<reaction metaid="re52" id="re52" reversible="false" fast="false">
<annotation/>
<listOfReactants>
<speciesReference metaid="CDMT00126" species="s68"/>
</listOfReactants>
<listOfProducts>
<speciesReference metaid="CDMT00127" species="s46"/>
</listOfProducts>
<kineticLaw metaid="CDMT00128">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<times/>
<ci> s68 </ci>
<ci> k1 </ci>
</apply>
</math>
<listOfParameters>
<parameter metaid="CDMT00129" id="k1" name="k1" value="0.01" units="substance"/>
</listOfParameters>
</kineticLaw>
</reaction>
<reaction metaid="re55" id="re55" reversible="false" fast="false">
<annotation/>
<listOfReactants>
<speciesReference metaid="CDMT00130" species="s46"/>
</listOfReactants>
<listOfProducts>
<speciesReference metaid="CDMT00131" species="s72"/>
</listOfProducts>
<kineticLaw metaid="CDMT00132">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<times/>
<ci> s46 </ci>
<ci> k1 </ci>
</apply>
</math>
<listOfParameters>
<parameter metaid="CDMT00133" id="k1" name="k1" value="0.01" units="substance"/>
</listOfParameters>
</kineticLaw>
</reaction>
<reaction metaid="re56" id="re56" reversible="false" fast="false">
<annotation/>
<listOfReactants>
<speciesReference metaid="CDMT00134" species="s72"/>
</listOfReactants>
<listOfProducts>
<speciesReference metaid="CDMT00135" species="s73"/>
</listOfProducts>
<kineticLaw metaid="CDMT00136">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<times/>
<ci> s72 </ci>
<ci> k1 </ci>
</apply>
</math>
<listOfParameters>
<parameter metaid="CDMT00137" id="k1" name="k1" value="0.1" units="substance"/>
</listOfParameters>
</kineticLaw>
</reaction>
<reaction metaid="re57" id="re57" reversible="false" fast="false">
<annotation/>
<listOfReactants>
<speciesReference metaid="CDMT00138" species="s73"/>
</listOfReactants>
<listOfProducts>
<speciesReference metaid="CDMT00139" species="s74"/>
</listOfProducts>
<kineticLaw metaid="CDMT00140">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<times/>
<ci> s73 </ci>
<ci> k1 </ci>
</apply>
</math>
<listOfParameters>
<parameter metaid="CDMT00141" id="k1" name="k1" value="0.1" units="substance"/>
</listOfParameters>
</kineticLaw>
</reaction>
<reaction metaid="re58" id="re58" reversible="false" fast="false">
<annotation/>
<listOfReactants>
<speciesReference metaid="CDMT00142" species="s74"/>
</listOfReactants>
<listOfProducts>
<speciesReference metaid="CDMT00143" species="s76"/>
</listOfProducts>
<kineticLaw metaid="CDMT00144">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<times/>
<ci> s74 </ci>
<ci> k1 </ci>
</apply>
</math>
<listOfParameters>
<parameter metaid="CDMT00145" id="k1" name="k1" value="0.1" units="substance"/>
</listOfParameters>
</kineticLaw>
</reaction>
<reaction metaid="re59" id="re59" reversible="false" fast="false">
<annotation/>
<listOfReactants>
<speciesReference metaid="CDMT00146" species="s73"/>
</listOfReactants>
<listOfProducts>
<speciesReference metaid="CDMT00147" species="s88"/>
</listOfProducts>
<kineticLaw metaid="CDMT00148">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<times/>
<ci> s73 </ci>
<ci> k1 </ci>
</apply>
</math>
<listOfParameters>
<parameter metaid="CDMT00149" id="k1" name="k1" value="0.1" units="substance"/>
</listOfParameters>
</kineticLaw>
</reaction>
<reaction metaid="re60" id="re60" reversible="false" fast="false">
<annotation/>
<listOfReactants>
<speciesReference metaid="CDMT00150" species="s88"/>
</listOfReactants>
<listOfProducts>
<speciesReference metaid="CDMT00151" species="s89"/>
</listOfProducts>
<kineticLaw metaid="CDMT00152">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<times/>
<ci> s88 </ci>
<ci> k1 </ci>
</apply>
</math>
<listOfParameters>
<parameter metaid="CDMT00153" id="k1" name="k1" value="0.1" units="substance"/>
</listOfParameters>
</kineticLaw>
</reaction>
<reaction metaid="re61" id="re61" reversible="false" fast="false">
<annotation/>
<listOfReactants>
<speciesReference metaid="CDMT00154" species="s89"/>
</listOfReactants>
<listOfProducts>
<speciesReference metaid="CDMT00155" species="s76"/>
</listOfProducts>
<kineticLaw metaid="CDMT00156">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<times/>
<ci> s89 </ci>
<ci> k1 </ci>
</apply>
</math>
<listOfParameters>
<parameter metaid="CDMT00157" id="k1" name="k1" value="0.1" units="substance"/>
</listOfParameters>
</kineticLaw>
</reaction>
<reaction metaid="re62" id="re62" reversible="false" fast="false">
<annotation/>
<listOfReactants>
<speciesReference metaid="CDMT00158" species="s88"/>
</listOfReactants>
<listOfProducts>
<speciesReference metaid="CDMT00159" species="s90"/>
</listOfProducts>
<kineticLaw metaid="CDMT00160">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<times/>
<ci> s88 </ci>
<ci> k1 </ci>
</apply>
</math>
<listOfParameters>
<parameter metaid="CDMT00161" id="k1" name="k1" value="0.1" units="substance"/>
</listOfParameters>
</kineticLaw>
</reaction>
<reaction metaid="re64" id="re64" reversible="false" fast="false">
<annotation/>
<listOfReactants>
<speciesReference metaid="CDMT00162" species="s90"/>
</listOfReactants>
<listOfProducts>
<speciesReference metaid="CDMT00163" species="s76"/>
</listOfProducts>
<kineticLaw metaid="CDMT00164">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<times/>
<ci> s90 </ci>
<ci> k1 </ci>
</apply>
</math>
<listOfParameters>
<parameter metaid="CDMT00165" id="k1" name="k1" value="0.1" units="substance"/>
</listOfParameters>
</kineticLaw>
</reaction>
<reaction metaid="re65" id="re65" reversible="false" fast="false">
<annotation/>
<listOfReactants>
<speciesReference metaid="CDMT00166" species="s55"/>
</listOfReactants>
<listOfProducts>
<speciesReference metaid="CDMT00167" species="s92"/>
</listOfProducts>
<kineticLaw metaid="CDMT00168">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<times/>
<ci> s55 </ci>
<ci> k1 </ci>
</apply>
</math>
<listOfParameters>
<parameter metaid="CDMT00169" id="k1" name="k1" value="0.0001" units="substance"/>
</listOfParameters>
</kineticLaw>
</reaction>
<reaction metaid="re66" id="re66" reversible="false" fast="false">
<annotation/>
<listOfReactants>
<speciesReference metaid="CDMT00170" species="s91"/>
</listOfReactants>
<listOfProducts>
<speciesReference metaid="CDMT00171" species="s20"/>
</listOfProducts>
<kineticLaw metaid="CDMT00172">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<times/>
<ci> s91 </ci>
<ci> k1 </ci>
</apply>
</math>
<listOfParameters>
<parameter metaid="CDMT00173" id="k1" name="k1" value="0.1" units="substance"/>
</listOfParameters>
</kineticLaw>
</reaction>
</listOfReactions>
</model>
</sbml>

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