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ALS_SBML__v0.xml
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ALS_SBML__v0.xml
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<?xml version='1.0' encoding='UTF-8' standalone='no'?>
<sbml xmlns="http://www.sbml.org/sbml/level2/version4" level="2" metaid="c4124f17-ac90-4ca4-be1d-2fe34c562a24" version="4">
<model name="JPLeRouzic2018 - Interaction between astrocytes and neurons in Amyotrophic lateral sclerosis (ALS)" id="MODEL_to_be_done">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
<div class="dc:title">JPLeRouzic2018 - Interactions between astrocytes
and neurons in Amyotrophic lateral sclerosis (ALS)</div>
<div class="dc:description">Encoded non-curated model. Issues: <br>To be done</br>
</div>
<div class="dc:bibliographicCitation"> <p>This model is described in the article:</p>
<div class="bibo:title"> <a href="http://identifiers.org/pubmed/20552235" title="Access to this publication">Motor neuron-immune interactions: The vicious circle of ALS.</a>
</div>
<div class="bibo:authorList">Barbeito AG, Mesci P, Boillée S.</div>
<div class="bibo:Journal">J Neural Transm (Vienna). 2010 Aug;117(8):981-1000.</div>
<p>Abstract:</p>
<div class="bibo:abstract"> <p>Because microglial cells, the resident macrophages of the CNS, react to any lesion of the nervous system, <br/>
they have for long been regarded as potential players in the pathogenesis of several neurodegenerative disorders including amyotrophic lateral sclerosis, <br/>
the most common motor neuron disease in the adult. <br/>
In recent years, this microglial reaction to motor neuron injury, in particular, and the innate immune response, in general, <br/>
has been implicated in the progression of the disease, in mouse models of ALS. <br/>
The mechanisms by which microglial cells influence motor neuron death in ALS are still largely unknown. <br/>
Microglial activation increases over the course of the disease and is associated with an alteration in the production of toxic factors and also <br/>
neurotrophic factors. <br/>
Adding to the microglial/macrophage response to motor neuron degeneration, the adaptive immune system can likewise influence the disease process. <br/>
Exploring these motor neuron-immune interactions could lead to a better understanding in the physiopathology of ALS to find <br/>
new pathways to slow down motor neuron degeneration. </p>
</div>
<div class="dc:publisher"> <p>This model will be hosted on <a href="http://www.ebi.ac.uk/biomodels/">BioModels Database</a>
and identified by: <a href="http://identifiers.org/biomodels.db/MODELtobedone">MODEL-to-be-done</a>
. </p>
<p>To cite BioModels Database, please use: <a href="http://identifiers.org/pubmed/20587024" title="Latest BioModels Database publication">BioModels Database:
An enhanced, curated and annotated resource for published
quantitative kinetic models</a>
. </p>
</div>
<div class="dc:license"> <p>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 <a href="http://creativecommons.org/publicdomain/zero/1.0/" title="Access to: CC0 1.0 Universal (CC0 1.0), Public Domain Dedication">CC0
Public Domain Dedication</a>
for more information. </p>
</div>
</div>
</body>
</notes>
<listOfUnitDefinitions>
<unitDefinition name="volume" id="volume" metaid="_38ba8c9f-937c-475c-813f-aa6ade0b1845">
<listOfUnits>
<unit scale="-3" metaid="a9cd72a6-2891-4f4a-99ce-1de794afd9c0" kind="litre" multiplier="1" exponent="1"/>
</listOfUnits>
</unitDefinition>
<unitDefinition name="time" id="time" metaid="_79bb7d94-2052-4d38-801e-f2de2f2cf67a">
<listOfUnits>
<unit scale="0" metaid="d517ee51-ff20-4f36-89a5-72cc7414e9c1" kind="second" exponent="1"/>
</listOfUnits>
</unitDefinition>
<unitDefinition name="substance" id="substance" metaid="_45963f6f-46e8-415f-83b9-f4ff8374d6fb">
<listOfUnits>
<unit scale="0" metaid="_80760473-3d2d-49a5-853b-c0db9933eb5d" kind="dimensionless" multiplier="1" exponent="1"/>
</listOfUnits>
</unitDefinition>
</listOfUnitDefinitions>
<listOfCompartments>
<compartment constant="true" size="1" metaid="COPASI1" name="CentralNervousSystem" id="CentralNervousSystem" spatialDimensions="3"/>
<compartment constant="true" size="0.2" metaid="_9900a077-72fa-46e3-9b6c-81856a5bdb48" name="Extracellular space" id="Extracellular_space" spatialDimensions="3"/>
<compartment constant="true" size="0.0055" metaid="_15807251-6568-48ac-8f23-b56570441672" name="Capillaries" id="Capillaries" spatialDimensions="3"/>
<compartment constant="true" size="0.0237" metaid="dd33450c-6095-4d8e-9482-3ad351480412" name="Veins" id="Veins" spatialDimensions="3"/>
</listOfCompartments>
<listOfSpecies>
<species boundaryCondition="true" constant="false" metaid="COPASI211" hasOnlySubstanceUnits="false" compartment="CentralNervousSystem" name="PreSynapticNeurons" id="PreSynapticNeurons" initialConcentration="999999">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
<pre>Pre-Synaptic Neurons</pre>
</body>
</notes>
</species>
<species boundaryCondition="true" constant="false" metaid="COPASI212" hasOnlySubstanceUnits="false" compartment="CentralNervousSystem" name="Exocytosis" id="Exocytosis" initialConcentration="999999">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
<pre>Exocytosis</pre>
</body>
</notes>
</species>
<species boundaryCondition="true" constant="false" metaid="COPASI213" hasOnlySubstanceUnits="false" compartment="CentralNervousSystem" name="BrokenMotorUnit" id="BrokenMotorUnit" initialConcentration="1">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
A motor unit is made up of a motor neuron and the skeletal muscle fibers innervated by that motor neuron's axonal terminals.<br/>
Groups of motor units often work together to coordinate the contractions of a single muscle.<br/>
All of the motor units within a muscle are considered a motor pool. </body>
</notes>
</species>
<species boundaryCondition="true" constant="false" metaid="COPASI214" hasOnlySubstanceUnits="false" compartment="CentralNervousSystem" name="LivingUpperMotoNeurons" id="LivingUpperMotoNeurons" initialConcentration="999999">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
Surviving Upper neurons<br/>
Upper motor neurons are found in the brain and carry motor information down the spinal cord to activate the lower motor neurons,
</body>
</notes>
</species>
<species boundaryCondition="true" constant="false" metaid="COPASI311" hasOnlySubstanceUnits="false" compartment="CentralNervousSystem" name="DeadUpperMotoNeurons" id="DeadUpperMotoNeurons" initialConcentration="1">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
Dead Upper neurons<br/>
Upper motor neurons are found in the brain and carry motor information down the spinal cord to activate the lower motor neurons,
</body>
</notes>
</species>
<species boundaryCondition="true" constant="false" metaid="COPASI215" hasOnlySubstanceUnits="false" compartment="CentralNervousSystem" name="LivingLowerMotoNeurons" id="LivingLowerMotoNeurons" initialConcentration="999999">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
Surviving lower motor neurons<br/>
The efferent fiber carries nerve impulses away from the the spinal cord, and toward the muscles.<br/>
</body>
</notes>
</species>
<species boundaryCondition="true" constant="false" metaid="COPASI312" hasOnlySubstanceUnits="false" compartment="CentralNervousSystem" name="DeadLowerMotoNeurons" id="DeadLowerMotoNeurons" initialConcentration="1">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
Dead lower motor neurons<br/>
The efferent fiber carries nerve impulses away from the the spinal cord, and toward the muscles.<br/>
</body>
</notes>
</species>
<species boundaryCondition="true" constant="false" metaid="COPASI411" hasOnlySubstanceUnits="false" compartment="CentralNervousSystem" name="Non_Inflammatory_Astroglia" id="Non_Inflammatory_Astroglia" initialConcentration="200">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
<pre>Quiescent astroglia</pre>
</body>
</notes>
</species>
<species boundaryCondition="true" constant="false" metaid="COPASI511" hasOnlySubstanceUnits="false" compartment="CentralNervousSystem" name="Pro_Inflammatory_Astroglia" id="Pro_Inflammatory_Astroglia" initialConcentration="50">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
<pre>Proliferating astroglia</pre>
</body>
</notes>
</species>
<species boundaryCondition="true" constant="false" metaid="COPASI611" hasOnlySubstanceUnits="false" compartment="CentralNervousSystem" name="Anti_Inflammatory_Microglia" id="Anti_Inflammatory_Microglia" initialConcentration="200">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
<pre>Normal microglia</pre>
</body>
</notes>
</species>
<species boundaryCondition="true" constant="false" metaid="COPASI711" hasOnlySubstanceUnits="false" compartment="CentralNervousSystem" name="Pro_Inflammatory_Microglia" id="Pro_Inflammatory_Microglia" initialConcentration="50">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
<pre>Reactive microglia</pre>
</body>
</notes>
</species>
<species boundaryCondition="true" constant="false" metaid="COPASI2511" hasOnlySubstanceUnits="false" compartment="CentralNervousSystem" name="Monocyte" id="Monocyte" initialConcentration="1">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
They are the largest type of leukocyte and can differentiate into macrophages and myeloid lineage dendritic cells.<br/>
Monocytes can differentiate into dendritic cells by adding the cytokines granulocyte macrophage colony-stimulating factor (GM-CSF) and interleukin 4.
</body>
</notes>
</species>
<species boundaryCondition="true" constant="false" metaid="COPASI2211" hasOnlySubstanceUnits="false" compartment="CentralNervousSystem" name="B_Cell" id="B_Cell" initialConcentration="1">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
B cells, also known as B lymphocytes, are a type of white blood cell.<br/>
* They secrete antibodies.<br/>
* B cells are also classified as professional antigen-presenting cells (APCs)).<br/>
* B cells secrete cytokines.<br/>
</body>
</notes>
</species>
<species boundaryCondition="true" constant="false" metaid="COPASI2212" hasOnlySubstanceUnits="false" compartment="CentralNervousSystem" name="T_Cell" id="T_Cell" initialConcentration="1">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
T cell, or T lymphocyte, is a type of lymphocyte that plays a central role in cell-mediated immunity.<br/>
They mature in the thymus which "selects for" T cells capable of interacting with MHC, and kill the "non-self" cells.<br/>
On can further categorize T cells in:<br/>
* Cytotoxic T cells (CD8+ T cells)<br/>
* Helper T cells (CD4+ T cells)<br/>
* Regulatory T cells<br/>
* Natural Killer T cells
</body>
</notes>
</species>
<species boundaryCondition="true" constant="false" metaid="COPASI2213" hasOnlySubstanceUnits="false" compartment="CentralNervousSystem" name="DentriticCell" id="DentriticCell" initialConcentration="1">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
Dendritic cells are antigen-presenting cells. They process ("eat") material found in the ECM and present it to the T cells.<br/>
They act as messengers between the innate and the adaptive immune systems.
</body>
</notes>
</species>
<species boundaryCondition="true" constant="false" metaid="COPASI2311" hasOnlySubstanceUnits="false" compartment="CentralNervousSystem" name="Cytokines" id="Cytokines" initialConcentration="1">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
<pre>Cytokines</pre>
</body>
</notes>
</species>
<!-- Metabolism -->
</listOfSpecies>
<listOfParameters>
<parameter name="prmDeadNeurons" constant="true" id="prmDeadNeurons" value="1">
<notes>
Dead neurons
</notes>
</parameter>
<parameter name="prmLivingNeurons" constant="true" id="prmLivingNeurons" value="0.5">
<notes>
Living neurons
</notes>
</parameter>
<parameter name="prmProInflamMicroglia" constant="true" id="prmProInflamMicroglia" value="0">
<notes>
Pro Inflammatory Microglia
</notes>
</parameter>
<parameter name="prmAntiInflamMicroglia" constant="true" id="prmAntiInflamMicroglia" value="1">
<notes>
Anti Inflammatory Microglia
</notes>
</parameter>
<parameter name="prmProInflamAstroglia" constant="true" id="prmProInflamAstroglia" value="1">
<notes>
Pro Inflammatory Astroglia
</notes>
</parameter>
<parameter name="prmNonInflamAstroglia" constant="true" id="prmNonInflamAstroglia" value="0.5">
<notes>
Quiescent astroglia
</notes>
</parameter>
<parameter name="prmTxcAstroglia" constant="true" id="prmTxcAstroglia" value="20">
<notes>
Toxic output from astroglia
</notes>
</parameter>
<parameter name="prmTxcMicroglia" constant="true" id="prmTxcMicroglia" value="20">
<notes>
Toxic output from microglia
</notes>
</parameter>
<parameter name="prmCD4Lymphocytes" constant="true" id="prmCD4Lymphocytes" value="0.5">
<notes>
Controls the production of CD4 T_Lymphocytes in a dependency with the number of dying neurons
</notes>
</parameter>
<parameter name="prmCD8Lymphocytes" constant="true" id="prmCD8Lymphocytes" value="0.5">
<notes>
Controls the production of CD8 T_Lymphocytes in a dependency with the number of dying neurons
</notes>
</parameter>
<parameter name="Nb of neurons" id="NbOfNeurons" value="1000000">
<notes>
</notes>
</parameter>
<parameter name="Nb of microglia" id="NbOfMicroglia" value="100000">
<notes>
</notes>
</parameter>
<parameter name="Nb of astrocytes" id="NbOfAstrocytes" value="200000">
<notes>
</notes>
</parameter>
<!-- Metabolism -->
</listOfParameters>
<listOfRules>
<rateRule variable="DeadLowerMotoNeurons" metaid="db19c551-9a1b-4c4f-a22b-5cb828b14a48">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<times/>
<ci> NbOfNeurons </ci>
<apply>
<divide/>
<apply>
<plus/>
<apply>
<times/>
<ci> prmProInflamAstroglia </ci>
<ci> Pro_Inflammatory_Astroglia </ci>
</apply>
<apply>
<times/>
<ci> prmProInflamMicroglia </ci>
<ci> Pro_Inflammatory_Microglia </ci>
</apply>
</apply>
<apply>
<plus/>
<ci> NbOfAstrocytes </ci>
<ci> NbOfMicroglia </ci>
</apply>
</apply>
</apply>
</math>
</rateRule>
<rateRule variable="LivingLowerMotoNeurons" metaid="c7b7bcea-1097-42ef-8111-4023cebc0e75">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<minus/>
<ci> DeadLowerMotoNeurons </ci>
</apply>
</math>
</rateRule>
<rateRule variable="Non_Inflammatory_Astroglia" metaid="_16d08848-7c59-4497-9147-a2bc5389f6fa">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<minus/>
<apply>
<times/>
<ci> prmAntiInflamMicroglia </ci>
<ci> Anti_Inflammatory_Microglia </ci>
</apply>
<apply>
<times/>
<ci> prmProInflamAstroglia </ci>
<ci> Pro_Inflammatory_Microglia </ci>
</apply>
</apply>
</math>
</rateRule>
<rateRule variable="Pro_Inflammatory_Astroglia" metaid="_788b482c-008b-4d79-95da-96efe85f6032">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<times/>
<ci> prmProInflamMicroglia </ci>
<ci> Pro_Inflammatory_Microglia </ci>
</apply>
</math>
</rateRule>
<rateRule variable="Anti_Inflammatory_Microglia" metaid="fbad149e-46be-407f-97b8-f2f451c5fb42">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<minus/>
<apply>
<times/>
<ci> prmLivingNeurons </ci>
<ci> Non_Inflammatory_Astroglia </ci>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci> prmDeadNeurons </ci>
<ci> DeadLowerMotoNeurons </ci>
</apply>
<cn type="integer"> 10 </cn>
</apply>
</apply>
</math>
</rateRule>
<rateRule variable="Pro_Inflammatory_Microglia" metaid="_88860791-365a-4268-9a37-235173f8db38">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<ci> DeadLowerMotoNeurons </ci>
</math>
</rateRule>
<rateRule variable="CD4_T_Lymphocytes">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<times/>
<ci> prmCD4Lymphocytes </ci>
<ci> DeadLowerMotoNeurons </ci>
</apply>
</math>
</rateRule>
<rateRule variable="CD8_T_Lymphocytes">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<times/>
<ci> prmCD8Lymphocytes </ci>
<ci> DeadLowerMotoNeurons </ci>
</apply>
</math>
</rateRule>
<rateRule variable="ToxicFactors_Astroglia">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<times/>
<ci> prmProInflamAstroglia </ci>
<ci> Pro_Inflammatory_Astroglia </ci>
</apply>
</math>
</rateRule>
<rateRule variable="ToxicFactors_Microglia">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<times/>
<ci> prmProInflamMicroglia </ci>
<ci> Pro_Inflammatory_Microglia </ci>
</apply>
</math>
</rateRule>
<!-- Part about metabolism -->
</listOfRules>
</model>
</sbml>