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BIOMD0000000575 - Sass2009 - Approach to an α-synuclein-based BST model of Parkinson's disease

 

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Reference Publication
Publication ID: 19136028
Sass MB, Lorenz AN, Green RL, Coleman RA.
A pragmatic approach to biochemical systems theory applied to an alpha-synuclein-based model of Parkinson's disease.
J. Neurosci. Methods 2009 Apr; 178(2): 366-377
Department of Chemistry, Integrated Science Center, The College of William and Mary, Williamsburg, VA 23187, USA.  [more]
Model
Original Model: BIOMD0000000575.origin
Submitter: Audald Lloret i Villas
Submission ID: MODEL1504130001
Submission Date: 13 Apr 2015 15:55:01 UTC
Last Modification Date: 14 Apr 2015 15:38:41 UTC
Creation Date: 13 Apr 2015 18:26:08 UTC
Encoders:  Audald Lloret i Villas
set #1
bqbiol:hasProperty Human Disease Ontology Parkinson's disease
set #2
bqbiol:isVersionOf Gene Ontology dopamine metabolic process
Gene Ontology proteasome-mediated ubiquitin-dependent protein catabolic process
Gene Ontology chaperone-mediated autophagy
Gene Ontology macroautophagy
Gene Ontology inclusion body assembly
set #3
bqbiol:hasTaxon Taxonomy Homo sapiens
Notes
Sass2009 - Approach to an α-synuclein-based BST model of Parkinson's disease

This model is described in the article:

Sass MB, Lorenz AN, Green RL, Coleman RA.
J. Neurosci. Methods 2009 Apr; 178(2): 366-377

Abstract:

This paper presents a detailed systems model of Parkinson's disease (PD), developed utilizing a pragmatic application of biochemical systems theory (BST) intended to assist experimentalists in the study of system behavior. This approach utilizes relative values as a reasonable initial estimate for BST and provides a theoretical means of applying numerical solutions to qualitative and semi-quantitative understandings of cellular pathways and mechanisms. The approach allows for the simulation of human disease through its ability to organize and integrate existing information about metabolic pathways without having a full quantitative description of those pathways, so that hypotheses about individual processes may be tested in a systems environment. Incorporating this method, the PD model describes alpha-synuclein aggregation as mediated by dopamine metabolism, the ubiquitin-proteasome system, and lysosomal degradation, allowing for the examination of dynamic pathway interactions and the evaluation of possible toxic mechanisms in the aggregation process. Four system perturbations: elevated alpha-synuclein aggregation, impaired dopamine packaging, increased neurotoxins, and alpha-synuclein overexpression, were analyzed for correlation to qualitative PD system hypotheses present in the literature, with the model demonstrating a high level of agreement with these hypotheses. Additionally, various PD treatment methods, including levadopa and monoamine oxidase inhibition (MAOI) therapy, were applied to the disease models to examine their effects on the system. Future additions and refinements to the model may further the understanding of the emergent behaviors of the disease, helping in the identification of system sensitivities and possible therapeutic targets.

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.

Model
Publication ID: 19136028 Submission Date: 13 Apr 2015 15:55:01 UTC Last Modification Date: 14 Apr 2015 15:38:41 UTC Creation Date: 13 Apr 2015 18:26:08 UTC
Mathematical expressions
Reactions
J1 J2 J3 J4
J6 J7 J8 J9
J10 J11 J13 J14
J15 J16 J17 J18
J19 J20 J21 J22
J23 J24 J25 J26f
J26r J27f J27r J28f
J28r J29 J30 J31
J32 J33 J34 J35
J36 J37 J38 J43
J44 J45 J46 J47
J48 J50 J51 J52
J53 J54 J55 J56
J57 J100 J101 J102
J115 J116    
Rules
Assignment Rule (variable: k1') Assignment Rule (variable: k2') Assignment Rule (variable: k4') Assignment Rule (variable: k13')
Assignment Rule (variable: k15') Assignment Rule (variable: k32') Assignment Rule (variable: k35') Assignment Rule (variable: k36')
Assignment Rule (variable: k38') Assignment Rule (variable: k46') Assignment Rule (variable: k47') Assignment Rule (variable: k48')
Rate Rule (variable: Fe2+)      
Physical entities
Compartments Species
Neuronal cytosol Protofibril Fibril Lewy_body
Dopamine OH- OH_radical
H2O2 DA_quinone Ubiquitin
E1 Ub-E1 UbcH8
UbcH8-Ub Parkin Parkin-sub
Parkin-synphilin-1 Parkin-synphilin-1-ub Parkin-sub-ub4
Fragments UCH-L1 L-Dopa
DOPAL DOPAC GSH
GSSG Fe2+ Fe3+
UbcH8ub2 UbcH8ub3 UbcH8ub4
UbcH13/Uev1a UbcH13/Uev1a-ub asyn-UCH-L1
asyn-ub Protofibril-UCH-L1 Protofibril-Ub
UCH-L1-asyn-ub4 Hsc70-asyn Hsc70-Protofibril
Hsc70-fibril Hsc70 DA-S-parkin
O2- DA-GSH Neuromelanin
Neuromelanin-ntox-Fe3+ Alpha_synuclein ATP
Synphilin-1 Substrate TH
L-Tyr CO2 Neurotoxins
Bioamines VMAT2 O2
MAO NH3 ALDH
NAD+ NADH Catalase
H2O Gluta_per Gluta_red
DDC Preautophagosome_membrane SOD
Cysteine    
Vesicle V-DA V-ntox-ba Vesicle
     
Autophagosome Autophagosome    
Proteasome Proteasome    
Lysosome Lysosome    
Global parameters
g11 p186 p110 p19
p18 k1 g22 p286
p210 p29 p28 i26
k2 g326 g23 k3
k4 i41 i42 i43
g412 g415 g427 g430
k6 g613 g614 g615
k7 g715 g716 g717
k8 g819 g821 k9
g919 g920 k10 g1025
g1072 k11 g1124 g1170
k13 i131 i1310 g1335
g1336 g1351 k14 g1437
g1467 k15 i152 g156
g1544 g1545 k16 g1643
g1644 k17 g1742 g1744
k18 g186 g1851 k19
g196 g1951 g1953 g1960
k20 g209 g2065 k21
g2166 k22 g229 g2259
k23 g239 g2361 g2362
k24 g2463 g2464 k25
g2552 g2555 g2556 k26f
g26f15 g26f16 g26f18 k26r
g26r30 g26r68 k27f g27f15
g27f16 g27f68 k27r g27r30
g27r69 k28f g28f15 g28f16
g28f69 k28r g28r30 g28r70
k29 g2915 g2916 g2971
k30 g301 g3030 k31
g3172 g3173 k32 g321
p328 p329 p3210 p3286
g3274 k33 g332 g3330
k34 g3472 g3475 k35
g352 p358 p359 p3510
p3586 g3576 k36 i368
i369 i3610 i3686 g3677
g3679 k37 g3770 g3773
k38 i381 i382 i383
g3812 g3815 g3830 g3878
k43 g431 g4384 k44
g442 g4484 k45 g453
g4584 k46 i468 i469
i4610 i4686 g4677 g4681
k47 i478 i479 i4710
i4786 g4777 g4782 k48
i488 i489 i4810 i4886
g4877 g4883 k50 g501
g5080 k51 g512 g5180
k52 g523 g5280 k53
g534 g5380 k54 g5410
g5419 k55 g556 g5586
k56 g5686 g5687 k57
g5710 g5762 k100 g10037
g10051 g100115 k101 g10136
g10151 g101115 k102 g10210
g10251 g102115 k115 g11565
g11566 g115118 k116 g11642
g116118 k1' k2' k4'
k13' k15' k32' k35'
k36' k38' k46' k47'
k48'      
Reactions (58)
 
 J1 [Alpha_synuclein] → [Protofibril];   {Alpha_synuclein} , {Alpha_synuclein} , {Alpha_synuclein} , {Alpha_synuclein} , {Alpha_synuclein} , {Alpha_synuclein} , {Alpha_synuclein} , {Alpha_synuclein} , {Alpha_synuclein}
 
 J2 [Protofibril] → [Fibril];   {Protofibril} , {Protofibril} , {Protofibril} , {Protofibril} , {Protofibril} , {Protofibril} , {Protofibril} , {Protofibril} , {Protofibril}
 
 J3 [Fibril] + [Parkin-synphilin-1-ub] → [Lewy_body];   {Fibril} , {Parkin-synphilin-1-ub} , {Fibril} , {Parkin-synphilin-1-ub} , {Fibril} , {Parkin-synphilin-1-ub} , {Fibril} , {Parkin-synphilin-1-ub} , {Fibril} , {Parkin-synphilin-1-ub} , {Fibril} , {Parkin-synphilin-1-ub} , {Fibril} , {Parkin-synphilin-1-ub} , {Fibril} , {Parkin-synphilin-1-ub} , {Fibril} , {Parkin-synphilin-1-ub}
 
 J4 [Parkin-sub-ub4] → [Parkin] + [Fragments] + 4.0 × [Ubiquitin];   {Proteasome} , {ATP} , {UCH-L1} , {Parkin-sub-ub4} , {Proteasome} , {ATP} , {UCH-L1} , {Parkin-sub-ub4} , {Proteasome} , {ATP} , {UCH-L1} , {Parkin-sub-ub4} , {Proteasome} , {ATP} , {UCH-L1} , {Parkin-sub-ub4} , {Proteasome} , {ATP} , {UCH-L1} , {Parkin-sub-ub4} , {Proteasome} , {ATP} , {UCH-L1} , {Parkin-sub-ub4} , {Proteasome} , {ATP} , {UCH-L1} , {Parkin-sub-ub4} , {Proteasome} , {ATP} , {UCH-L1} , {Parkin-sub-ub4} , {Proteasome} , {ATP} , {UCH-L1} , {Parkin-sub-ub4} , {Proteasome} , {ATP} , {UCH-L1}
 
 J6 [Ubiquitin] + [E1] → [Ub-E1];   {ATP} , {Ubiquitin} , {E1} , {ATP} , {Ubiquitin} , {E1} , {ATP} , {Ubiquitin} , {E1} , {ATP} , {Ubiquitin} , {E1} , {ATP} , {Ubiquitin} , {E1} , {ATP} , {Ubiquitin} , {E1} , {ATP} , {Ubiquitin} , {E1} , {ATP} , {Ubiquitin} , {E1} , {ATP} , {Ubiquitin} , {E1} , {ATP}
 
 J7 [Ub-E1] + [UbcH8] → [E1] + [UbcH8-Ub];   {ATP} , {Ub-E1} , {UbcH8} , {ATP} , {Ub-E1} , {UbcH8} , {ATP} , {Ub-E1} , {UbcH8} , {ATP} , {Ub-E1} , {UbcH8} , {ATP} , {Ub-E1} , {UbcH8} , {ATP} , {Ub-E1} , {UbcH8} , {ATP} , {Ub-E1} , {UbcH8} , {ATP} , {Ub-E1} , {UbcH8} , {ATP} , {Ub-E1} , {UbcH8} , {ATP}
 
 J8 [Parkin] + [Substrate] → [Parkin-sub];   {Parkin} , {Substrate} , {Parkin} , {Substrate} , {Parkin} , {Substrate} , {Parkin} , {Substrate} , {Parkin} , {Substrate} , {Parkin} , {Substrate} , {Parkin} , {Substrate} , {Parkin} , {Substrate} , {Parkin} , {Substrate}
 
 J9 [Parkin] + [Synphilin-1] → [Parkin-synphilin-1];   {Parkin} , {Synphilin-1} , {Parkin} , {Synphilin-1} , {Parkin} , {Synphilin-1} , {Parkin} , {Synphilin-1} , {Parkin} , {Synphilin-1} , {Parkin} , {Synphilin-1} , {Parkin} , {Synphilin-1} , {Parkin} , {Synphilin-1} , {Parkin} , {Synphilin-1}
 
 J10 [Parkin-synphilin-1] + [UbcH13/Uev1a-ub] → [Parkin-synphilin-1-ub] + [UbcH13/Uev1a];   {Parkin-synphilin-1} , {UbcH13/Uev1a-ub} , {Parkin-synphilin-1} , {UbcH13/Uev1a-ub} , {Parkin-synphilin-1} , {UbcH13/Uev1a-ub} , {Parkin-synphilin-1} , {UbcH13/Uev1a-ub} , {Parkin-synphilin-1} , {UbcH13/Uev1a-ub} , {Parkin-synphilin-1} , {UbcH13/Uev1a-ub} , {Parkin-synphilin-1} , {UbcH13/Uev1a-ub} , {Parkin-synphilin-1} , {UbcH13/Uev1a-ub} , {Parkin-synphilin-1} , {UbcH13/Uev1a-ub}
 
 J11 [Parkin-sub] + [UbcH8ub4] → [Parkin-sub-ub4] + [UbcH8];   {Parkin-sub} , {UbcH8ub4} , {Parkin-sub} , {UbcH8ub4} , {Parkin-sub} , {UbcH8ub4} , {Parkin-sub} , {UbcH8ub4} , {Parkin-sub} , {UbcH8ub4} , {Parkin-sub} , {UbcH8ub4} , {Parkin-sub} , {UbcH8ub4} , {Parkin-sub} , {UbcH8ub4} , {Parkin-sub} , {UbcH8ub4}
 
 J13 [L-Tyr] + [O2] → [L-Dopa];   {TH} , {L-Tyr} , {O2} , {TH} , {L-Tyr} , {O2} , {TH} , {L-Tyr} , {O2} , {TH} , {L-Tyr} , {O2} , {TH} , {L-Tyr} , {O2} , {TH} , {L-Tyr} , {O2} , {TH} , {L-Tyr} , {O2} , {TH} , {L-Tyr} , {O2} , {TH} , {L-Tyr} , {O2} , {TH}
 
 J14 [L-Dopa] → [Dopamine] + [CO2];   {DDC} , {L-Dopa} , {DDC} , {L-Dopa} , {DDC} , {L-Dopa} , {DDC} , {L-Dopa} , {DDC} , {L-Dopa} , {DDC} , {L-Dopa} , {DDC} , {L-Dopa} , {DDC} , {L-Dopa} , {DDC} , {L-Dopa} , {DDC}
 
 J15 [Dopamine] + [Vesicle] → [V-DA];   {VMAT2} , {Dopamine} , {Vesicle} , {VMAT2} , {Dopamine} , {Vesicle} , {VMAT2} , {Dopamine} , {Vesicle} , {VMAT2} , {Dopamine} , {Vesicle} , {VMAT2} , {Dopamine} , {Vesicle} , {VMAT2} , {Dopamine} , {Vesicle} , {VMAT2} , {Dopamine} , {Vesicle} , {VMAT2} , {Dopamine} , {Vesicle} , {VMAT2} , {Dopamine} , {Vesicle} , {VMAT2}
 
 J16 [Bioamines] + [Vesicle] → [V-ntox-ba];   {Bioamines} , {Vesicle} , {Bioamines} , {Vesicle} , {Bioamines} , {Vesicle} , {Bioamines} , {Vesicle} , {Bioamines} , {Vesicle} , {Bioamines} , {Vesicle} , {Bioamines} , {Vesicle} , {Bioamines} , {Vesicle} , {Bioamines} , {Vesicle}
 
 J17 [Neurotoxins] + [Vesicle] → [V-ntox-ba];   {Neurotoxins} , {Vesicle} , {Neurotoxins} , {Vesicle} , {Neurotoxins} , {Vesicle} , {Neurotoxins} , {Vesicle} , {Neurotoxins} , {Vesicle} , {Neurotoxins} , {Vesicle} , {Neurotoxins} , {Vesicle} , {Neurotoxins} , {Vesicle} , {Neurotoxins} , {Vesicle}
 
 J18 [Dopamine] + [O2] → [DA_quinone] + [O2-];   {Dopamine} , {O2} , {Dopamine} , {O2} , {Dopamine} , {O2} , {Dopamine} , {O2} , {Dopamine} , {O2} , {Dopamine} , {O2} , {Dopamine} , {O2} , {Dopamine} , {O2} , {Dopamine} , {O2}
 
 J19 [Dopamine] + [O2] + [H2O] → [NH3] + [DOPAL] + [H2O2];   {MAO} , {Dopamine} , {O2} , {H2O} , {MAO} , {Dopamine} , {O2} , {H2O} , {MAO} , {Dopamine} , {O2} , {H2O} , {MAO} , {Dopamine} , {O2} , {H2O} , {MAO} , {Dopamine} , {O2} , {H2O} , {MAO} , {Dopamine} , {O2} , {H2O} , {MAO} , {Dopamine} , {O2} , {H2O} , {MAO} , {Dopamine} , {O2} , {H2O} , {MAO} , {Dopamine} , {O2} , {H2O} , {MAO}
 
 J20 [H2O2] + [Fe2+] → [Fe3+] + [OH_radical] + [OH-];   {H2O2} , {Fe2+} , {H2O2} , {Fe2+} , {H2O2} , {Fe2+} , {H2O2} , {Fe2+} , {H2O2} , {Fe2+} , {H2O2} , {Fe2+} , {H2O2} , {Fe2+} , {H2O2} , {Fe2+} , {H2O2} , {Fe2+}
 
 J21 [Fe3+] → [Fe2+];   {Fe3+} , {Fe3+} , {Fe3+} , {Fe3+} , {Fe3+} , {Fe3+} , {Fe3+} , {Fe3+} , {Fe3+}
 
 J22 [H2O2] → [H2O] + [O2];   {Catalase} , {H2O2} , {Catalase} , {H2O2} , {Catalase} , {H2O2} , {Catalase} , {H2O2} , {Catalase} , {H2O2} , {Catalase} , {H2O2} , {Catalase} , {H2O2} , {Catalase} , {H2O2} , {Catalase} , {H2O2} , {Catalase}
 
 J23 [H2O2] + [GSH] → [H2O] + [GSSG];   {Gluta_per} , {H2O2} , {GSH} , {Gluta_per} , {H2O2} , {GSH} , {Gluta_per} , {H2O2} , {GSH} , {Gluta_per} , {H2O2} , {GSH} , {Gluta_per} , {H2O2} , {GSH} , {Gluta_per} , {H2O2} , {GSH} , {Gluta_per} , {H2O2} , {GSH} , {Gluta_per} , {H2O2} , {GSH} , {Gluta_per} , {H2O2} , {GSH} , {Gluta_per}
 
 J24 [GSSG] → [GSH];   {Gluta_red} , {GSSG} , {Gluta_red} , {GSSG} , {Gluta_red} , {GSSG} , {Gluta_red} , {GSSG} , {Gluta_red} , {GSSG} , {Gluta_red} , {GSSG} , {Gluta_red} , {GSSG} , {Gluta_red} , {GSSG} , {Gluta_red} , {GSSG} , {Gluta_red}
 
 J25 [DOPAL] + [NAD+] → [DOPAC] + [NADH];   {ALDH} , {DOPAL} , {NAD+} , {ALDH} , {DOPAL} , {NAD+} , {ALDH} , {DOPAL} , {NAD+} , {ALDH} , {DOPAL} , {NAD+} , {ALDH} , {DOPAL} , {NAD+} , {ALDH} , {DOPAL} , {NAD+} , {ALDH} , {DOPAL} , {NAD+} , {ALDH} , {DOPAL} , {NAD+} , {ALDH} , {DOPAL} , {NAD+} , {ALDH}
 
 J26f [Ub-E1] + [UbcH8-Ub] → [E1] + [UbcH8ub2];   {ATP} , {Ub-E1} , {UbcH8-Ub} , {ATP} , {Ub-E1} , {UbcH8-Ub} , {ATP} , {Ub-E1} , {UbcH8-Ub} , {ATP} , {Ub-E1} , {UbcH8-Ub} , {ATP} , {Ub-E1} , {UbcH8-Ub} , {ATP} , {Ub-E1} , {UbcH8-Ub} , {ATP} , {Ub-E1} , {UbcH8-Ub} , {ATP} , {Ub-E1} , {UbcH8-Ub} , {ATP} , {Ub-E1} , {UbcH8-Ub} , {ATP}
 
 J26r [UbcH8ub2] → [UbcH8] + 2.0 × [Ubiquitin];   {UCH-L1} , {UbcH8ub2} , {UCH-L1} , {UbcH8ub2} , {UCH-L1} , {UbcH8ub2} , {UCH-L1} , {UbcH8ub2} , {UCH-L1} , {UbcH8ub2} , {UCH-L1} , {UbcH8ub2} , {UCH-L1} , {UbcH8ub2} , {UCH-L1} , {UbcH8ub2} , {UCH-L1} , {UbcH8ub2} , {UCH-L1}
 
 J27f [Ub-E1] + [UbcH8ub2] → [E1] + [UbcH8ub3];   {ATP} , {Ub-E1} , {UbcH8ub2} , {ATP} , {Ub-E1} , {UbcH8ub2} , {ATP} , {Ub-E1} , {UbcH8ub2} , {ATP} , {Ub-E1} , {UbcH8ub2} , {ATP} , {Ub-E1} , {UbcH8ub2} , {ATP} , {Ub-E1} , {UbcH8ub2} , {ATP} , {Ub-E1} , {UbcH8ub2} , {ATP} , {Ub-E1} , {UbcH8ub2} , {ATP} , {Ub-E1} , {UbcH8ub2} , {ATP}
 
 J27r [UbcH8ub3] → [UbcH8] + 3.0 × [Ubiquitin];   {UCH-L1} , {UbcH8ub3} , {UCH-L1} , {UbcH8ub3} , {UCH-L1} , {UbcH8ub3} , {UCH-L1} , {UbcH8ub3} , {UCH-L1} , {UbcH8ub3} , {UCH-L1} , {UbcH8ub3} , {UCH-L1} , {UbcH8ub3} , {UCH-L1} , {UbcH8ub3} , {UCH-L1} , {UbcH8ub3} , {UCH-L1}
 
 J28f [Ub-E1] + [UbcH8ub3] → [E1] + [UbcH8ub4];   {ATP} , {Ub-E1} , {UbcH8ub3} , {ATP} , {Ub-E1} , {UbcH8ub3} , {ATP} , {Ub-E1} , {UbcH8ub3} , {ATP} , {Ub-E1} , {UbcH8ub3} , {ATP} , {Ub-E1} , {UbcH8ub3} , {ATP} , {Ub-E1} , {UbcH8ub3} , {ATP} , {Ub-E1} , {UbcH8ub3} , {ATP} , {Ub-E1} , {UbcH8ub3} , {ATP} , {Ub-E1} , {UbcH8ub3} , {ATP}
 
 J28r [UbcH8ub4] → [UbcH8] + 4.0 × [Ubiquitin];   {UCH-L1} , {UbcH8ub4} , {UCH-L1} , {UbcH8ub4} , {UCH-L1} , {UbcH8ub4} , {UCH-L1} , {UbcH8ub4} , {UCH-L1} , {UbcH8ub4} , {UCH-L1} , {UbcH8ub4} , {UCH-L1} , {UbcH8ub4} , {UCH-L1} , {UbcH8ub4} , {UCH-L1} , {UbcH8ub4} , {UCH-L1}
 
 J29 [Ub-E1] + [UbcH13/Uev1a] → [E1] + [UbcH13/Uev1a-ub];   {ATP} , {Ub-E1} , {UbcH13/Uev1a} , {ATP} , {Ub-E1} , {UbcH13/Uev1a} , {ATP} , {Ub-E1} , {UbcH13/Uev1a} , {ATP} , {Ub-E1} , {UbcH13/Uev1a} , {ATP} , {Ub-E1} , {UbcH13/Uev1a} , {ATP} , {Ub-E1} , {UbcH13/Uev1a} , {ATP} , {Ub-E1} , {UbcH13/Uev1a} , {ATP} , {Ub-E1} , {UbcH13/Uev1a} , {ATP} , {Ub-E1} , {UbcH13/Uev1a} , {ATP}
 
 J30 [Alpha_synuclein] + [UCH-L1] → [asyn-UCH-L1];   {Alpha_synuclein} , {UCH-L1} , {Alpha_synuclein} , {UCH-L1} , {Alpha_synuclein} , {UCH-L1} , {Alpha_synuclein} , {UCH-L1} , {Alpha_synuclein} , {UCH-L1} , {Alpha_synuclein} , {UCH-L1} , {Alpha_synuclein} , {UCH-L1} , {Alpha_synuclein} , {UCH-L1} , {Alpha_synuclein} , {UCH-L1}
 
 J31 [UbcH13/Uev1a-ub] + [asyn-UCH-L1] → [UbcH13/Uev1a] + [UCH-L1] + [asyn-ub];   {UbcH13/Uev1a-ub} , {asyn-UCH-L1} , {UbcH13/Uev1a-ub} , {asyn-UCH-L1} , {UbcH13/Uev1a-ub} , {asyn-UCH-L1} , {UbcH13/Uev1a-ub} , {asyn-UCH-L1} , {UbcH13/Uev1a-ub} , {asyn-UCH-L1} , {UbcH13/Uev1a-ub} , {asyn-UCH-L1} , {UbcH13/Uev1a-ub} , {asyn-UCH-L1} , {UbcH13/Uev1a-ub} , {asyn-UCH-L1} , {UbcH13/Uev1a-ub} , {asyn-UCH-L1}
 
 J32 [Alpha_synuclein] + [asyn-ub] → [Protofibril];   {Alpha_synuclein} , {asyn-ub} , {Alpha_synuclein} , {asyn-ub} , {Alpha_synuclein} , {asyn-ub} , {Alpha_synuclein} , {asyn-ub} , {Alpha_synuclein} , {asyn-ub} , {Alpha_synuclein} , {asyn-ub} , {Alpha_synuclein} , {asyn-ub} , {Alpha_synuclein} , {asyn-ub} , {Alpha_synuclein} , {asyn-ub}
 
 J33 [Protofibril] + [UCH-L1] → [Protofibril-UCH-L1];   {Protofibril} , {UCH-L1} , {Protofibril} , {UCH-L1} , {Protofibril} , {UCH-L1} , {Protofibril} , {UCH-L1} , {Protofibril} , {UCH-L1} , {Protofibril} , {UCH-L1} , {Protofibril} , {UCH-L1} , {Protofibril} , {UCH-L1} , {Protofibril} , {UCH-L1}
 
 J34 [UbcH13/Uev1a-ub] + [Protofibril-UCH-L1] → [UbcH13/Uev1a] + [UCH-L1] + [Protofibril-Ub];   {UbcH13/Uev1a-ub} , {Protofibril-UCH-L1} , {UbcH13/Uev1a-ub} , {Protofibril-UCH-L1} , {UbcH13/Uev1a-ub} , {Protofibril-UCH-L1} , {UbcH13/Uev1a-ub} , {Protofibril-UCH-L1} , {UbcH13/Uev1a-ub} , {Protofibril-UCH-L1} , {UbcH13/Uev1a-ub} , {Protofibril-UCH-L1} , {UbcH13/Uev1a-ub} , {Protofibril-UCH-L1} , {UbcH13/Uev1a-ub} , {Protofibril-UCH-L1} , {UbcH13/Uev1a-ub} , {Protofibril-UCH-L1}
 
 J35 [Protofibril] + [Protofibril-Ub] → [Fibril];   {Protofibril} , {Protofibril-Ub} , {Protofibril} , {Protofibril-Ub} , {Protofibril} , {Protofibril-Ub} , {Protofibril} , {Protofibril-Ub} , {Protofibril} , {Protofibril-Ub} , {Protofibril} , {Protofibril-Ub} , {Protofibril} , {Protofibril-Ub} , {Protofibril} , {Protofibril-Ub} , {Protofibril} , {Protofibril-Ub}
 
 J36 [Autophagosome] → [Fragments];   {Lysosome} , {Autophagosome} , {Lysosome} , {Autophagosome} , {Lysosome} , {Autophagosome} , {Lysosome} , {Autophagosome} , {Lysosome} , {Autophagosome} , {Lysosome} , {Autophagosome} , {Lysosome} , {Autophagosome} , {Lysosome} , {Autophagosome} , {Lysosome} , {Autophagosome} , {Lysosome}
 
 J37 [UbcH8ub4] + [asyn-UCH-L1] → [UCH-L1-asyn-ub4] + [UbcH8];   {UbcH8ub4} , {asyn-UCH-L1} , {UbcH8ub4} , {asyn-UCH-L1} , {UbcH8ub4} , {asyn-UCH-L1} , {UbcH8ub4} , {asyn-UCH-L1} , {UbcH8ub4} , {asyn-UCH-L1} , {UbcH8ub4} , {asyn-UCH-L1} , {UbcH8ub4} , {asyn-UCH-L1} , {UbcH8ub4} , {asyn-UCH-L1} , {UbcH8ub4} , {asyn-UCH-L1}
 
 J38 [UCH-L1-asyn-ub4] → [Fragments] + [UCH-L1] + 4.0 × [Ubiquitin];   {Proteasome} , {ATP} , {UCH-L1} , {UCH-L1-asyn-ub4} , {Proteasome} , {ATP} , {UCH-L1} , {UCH-L1-asyn-ub4} , {Proteasome} , {ATP} , {UCH-L1} , {UCH-L1-asyn-ub4} , {Proteasome} , {ATP} , {UCH-L1} , {UCH-L1-asyn-ub4} , {Proteasome} , {ATP} , {UCH-L1} , {UCH-L1-asyn-ub4} , {Proteasome} , {ATP} , {UCH-L1} , {UCH-L1-asyn-ub4} , {Proteasome} , {ATP} , {UCH-L1} , {UCH-L1-asyn-ub4} , {Proteasome} , {ATP} , {UCH-L1} , {UCH-L1-asyn-ub4} , {Proteasome} , {ATP} , {UCH-L1} , {UCH-L1-asyn-ub4} , {Proteasome} , {ATP} , {UCH-L1}
 
 J43 [Alpha_synuclein] + [Hsc70] → [Hsc70-asyn];   {Alpha_synuclein} , {Hsc70} , {Alpha_synuclein} , {Hsc70} , {Alpha_synuclein} , {Hsc70} , {Alpha_synuclein} , {Hsc70} , {Alpha_synuclein} , {Hsc70} , {Alpha_synuclein} , {Hsc70} , {Alpha_synuclein} , {Hsc70} , {Alpha_synuclein} , {Hsc70} , {Alpha_synuclein} , {Hsc70}
 
 J44 [Protofibril] + [Hsc70] → [Hsc70-Protofibril];   {Protofibril} , {Hsc70} , {Protofibril} , {Hsc70} , {Protofibril} , {Hsc70} , {Protofibril} , {Hsc70} , {Protofibril} , {Hsc70} , {Protofibril} , {Hsc70} , {Protofibril} , {Hsc70} , {Protofibril} , {Hsc70} , {Protofibril} , {Hsc70}
 
 J45 [Fibril] + [Hsc70] → [Hsc70-fibril];   {Fibril} , {Hsc70} , {Fibril} , {Hsc70} , {Fibril} , {Hsc70} , {Fibril} , {Hsc70} , {Fibril} , {Hsc70} , {Fibril} , {Hsc70} , {Fibril} , {Hsc70} , {Fibril} , {Hsc70} , {Fibril} , {Hsc70}
 
 J46 [Hsc70-asyn] → [Hsc70] + [Fragments];   {Lysosome} , {Hsc70-asyn} , {Lysosome} , {Hsc70-asyn} , {Lysosome} , {Hsc70-asyn} , {Lysosome} , {Hsc70-asyn} , {Lysosome} , {Hsc70-asyn} , {Lysosome} , {Hsc70-asyn} , {Lysosome} , {Hsc70-asyn} , {Lysosome} , {Hsc70-asyn} , {Lysosome} , {Hsc70-asyn} , {Lysosome}
 
 J47 [Hsc70-Protofibril] → [Hsc70] + [Fragments];   {Lysosome} , {Hsc70-Protofibril} , {Lysosome} , {Hsc70-Protofibril} , {Lysosome} , {Hsc70-Protofibril} , {Lysosome} , {Hsc70-Protofibril} , {Lysosome} , {Hsc70-Protofibril} , {Lysosome} , {Hsc70-Protofibril} , {Lysosome} , {Hsc70-Protofibril} , {Lysosome} , {Hsc70-Protofibril} , {Lysosome} , {Hsc70-Protofibril} , {Lysosome}
 
 J48 [Hsc70-fibril] → [Hsc70] + [Fragments];   {Lysosome} , {Hsc70-fibril} , {Lysosome} , {Hsc70-fibril} , {Lysosome} , {Hsc70-fibril} , {Lysosome} , {Hsc70-fibril} , {Lysosome} , {Hsc70-fibril} , {Lysosome} , {Hsc70-fibril} , {Lysosome} , {Hsc70-fibril} , {Lysosome} , {Hsc70-fibril} , {Lysosome} , {Hsc70-fibril} , {Lysosome}
 
 J50 [Alpha_synuclein] + [Preautophagosome_membrane] → [Autophagosome];   {Alpha_synuclein} , {Preautophagosome_membrane} , {Alpha_synuclein} , {Preautophagosome_membrane} , {Alpha_synuclein} , {Preautophagosome_membrane} , {Alpha_synuclein} , {Preautophagosome_membrane} , {Alpha_synuclein} , {Preautophagosome_membrane} , {Alpha_synuclein} , {Preautophagosome_membrane} , {Alpha_synuclein} , {Preautophagosome_membrane} , {Alpha_synuclein} , {Preautophagosome_membrane} , {Alpha_synuclein} , {Preautophagosome_membrane}
 
 J51 [Protofibril] + [Preautophagosome_membrane] → [Autophagosome];   {Protofibril} , {Preautophagosome_membrane} , {Protofibril} , {Preautophagosome_membrane} , {Protofibril} , {Preautophagosome_membrane} , {Protofibril} , {Preautophagosome_membrane} , {Protofibril} , {Preautophagosome_membrane} , {Protofibril} , {Preautophagosome_membrane} , {Protofibril} , {Preautophagosome_membrane} , {Protofibril} , {Preautophagosome_membrane} , {Protofibril} , {Preautophagosome_membrane}
 
 J52 [Fibril] + [Preautophagosome_membrane] → [Autophagosome];   {Fibril} , {Preautophagosome_membrane} , {Fibril} , {Preautophagosome_membrane} , {Fibril} , {Preautophagosome_membrane} , {Fibril} , {Preautophagosome_membrane} , {Fibril} , {Preautophagosome_membrane} , {Fibril} , {Preautophagosome_membrane} , {Fibril} , {Preautophagosome_membrane} , {Fibril} , {Preautophagosome_membrane} , {Fibril} , {Preautophagosome_membrane}
 
 J53 [Lewy_body] + [Preautophagosome_membrane] → [Autophagosome];   {Lewy_body} , {Preautophagosome_membrane} , {Lewy_body} , {Preautophagosome_membrane} , {Lewy_body} , {Preautophagosome_membrane} , {Lewy_body} , {Preautophagosome_membrane} , {Lewy_body} , {Preautophagosome_membrane} , {Lewy_body} , {Preautophagosome_membrane} , {Lewy_body} , {Preautophagosome_membrane} , {Lewy_body} , {Preautophagosome_membrane} , {Lewy_body} , {Preautophagosome_membrane}
 
 J54 [DA_quinone] + [Parkin] → [DA-S-parkin];   {DA_quinone} , {Parkin} , {DA_quinone} , {Parkin} , {DA_quinone} , {Parkin} , {DA_quinone} , {Parkin} , {DA_quinone} , {Parkin} , {DA_quinone} , {Parkin} , {DA_quinone} , {Parkin} , {DA_quinone} , {Parkin} , {DA_quinone} , {Parkin}
 
 J55 [Dopamine] + [O2-] → [H2O2] + [DA_quinone];   {Dopamine} , {O2-} , {Dopamine} , {O2-} , {Dopamine} , {O2-} , {Dopamine} , {O2-} , {Dopamine} , {O2-} , {Dopamine} , {O2-} , {Dopamine} , {O2-} , {Dopamine} , {O2-} , {Dopamine} , {O2-}
 
 J56 [O2-] → [H2O2] + [O2];   {SOD} , {O2-} , {SOD} , {O2-} , {SOD} , {O2-} , {SOD} , {O2-} , {SOD} , {O2-} , {SOD} , {O2-} , {SOD} , {O2-} , {SOD} , {O2-} , {SOD} , {O2-} , {SOD}
 
 J57 [DA_quinone] + [GSH] → [DA-GSH];   {DA_quinone} , {GSH} , {DA_quinone} , {GSH} , {DA_quinone} , {GSH} , {DA_quinone} , {GSH} , {DA_quinone} , {GSH} , {DA_quinone} , {GSH} , {DA_quinone} , {GSH} , {DA_quinone} , {GSH} , {DA_quinone} , {GSH}
 
 J100 [L-Dopa] + [O2] + [Cysteine] → [Neuromelanin] + [H2O2] + [CO2];   {L-Dopa} , {O2} , {Cysteine} , {L-Dopa} , {O2} , {Cysteine} , {L-Dopa} , {O2} , {Cysteine} , {L-Dopa} , {O2} , {Cysteine} , {L-Dopa} , {O2} , {Cysteine} , {L-Dopa} , {O2} , {Cysteine} , {L-Dopa} , {O2} , {Cysteine} , {L-Dopa} , {O2} , {Cysteine} , {L-Dopa} , {O2} , {Cysteine}
 
 J101 [L-Tyr] + [O2] + [Cysteine] → [Neuromelanin] + [H2O2] + [CO2];   {L-Tyr} , {O2} , {Cysteine} , {L-Tyr} , {O2} , {Cysteine} , {L-Tyr} , {O2} , {Cysteine} , {L-Tyr} , {O2} , {Cysteine} , {L-Tyr} , {O2} , {Cysteine} , {L-Tyr} , {O2} , {Cysteine} , {L-Tyr} , {O2} , {Cysteine} , {L-Tyr} , {O2} , {Cysteine} , {L-Tyr} , {O2} , {Cysteine}
 
 J102 [DA_quinone] + [O2] + [Cysteine] → [Neuromelanin] + [CO2];   {DA_quinone} , {O2} , {Cysteine} , {DA_quinone} , {O2} , {Cysteine} , {DA_quinone} , {O2} , {Cysteine} , {DA_quinone} , {O2} , {Cysteine} , {DA_quinone} , {O2} , {Cysteine} , {DA_quinone} , {O2} , {Cysteine} , {DA_quinone} , {O2} , {Cysteine} , {DA_quinone} , {O2} , {Cysteine} , {DA_quinone} , {O2} , {Cysteine}
 
 J115 [Fe3+] + [Neuromelanin] → [Neuromelanin-ntox-Fe3+];   {Fe3+} , {Neuromelanin} , {Fe3+} , {Neuromelanin} , {Fe3+} , {Neuromelanin} , {Fe3+} , {Neuromelanin} , {Fe3+} , {Neuromelanin} , {Fe3+} , {Neuromelanin} , {Fe3+} , {Neuromelanin} , {Fe3+} , {Neuromelanin} , {Fe3+} , {Neuromelanin}
 
 J116 [Neuromelanin] + [Neurotoxins] → [Neuromelanin-ntox-Fe3+];   {Neuromelanin} , {Neurotoxins} , {Neuromelanin} , {Neurotoxins} , {Neuromelanin} , {Neurotoxins} , {Neuromelanin} , {Neurotoxins} , {Neuromelanin} , {Neurotoxins} , {Neuromelanin} , {Neurotoxins} , {Neuromelanin} , {Neurotoxins} , {Neuromelanin} , {Neurotoxins} , {Neuromelanin} , {Neurotoxins}
 
Rules (13)
 
 Assignment Rule (name: k1_0) k1' = 0.0003*(p18*OH_radical+p19*H2O2+p110*DA_quinone+p186*O2)
 
 Assignment Rule (name: k2_0) k2' = 0.0001*(i26*Dopamine+p28*OH_radical+p29*H2O2+p210*DA_quinone+p286*O2)
 
 Assignment Rule (name: k4_0) k4' = 0.009*(i41*Alpha_synuclein+i42*Protofibril+i43*Fibril)
 
 Assignment Rule (name: k13_0) k13' = 0.001*(i131*Alpha_synuclein+i1310*DA_quinone)
 
 Assignment Rule (name: k15_0) k15' = 0.002*i152*Protofibril
 
 Assignment Rule (name: k32_0) k32' = 1E-5*(p328*OH_radical+p329*H2O2+p3210*DA_quinone+p3286*O2)
 
 Assignment Rule (name: k35_0) k35' = 1E-5*(p358*OH_radical+p359*H2O2+p3510*DA_quinone+p3586*O2)
 
 Assignment Rule (name: k36_0) k36' = 0.0005*(i368*OH_radical+i369*H2O2+i3610*DA_quinone+i3686*O2)
 
 Assignment Rule (name: k38_0) k38' = 0.007*(i381*Alpha_synuclein+i382*Protofibril+i383*Fibril)
 
 Assignment Rule (name: k46_0) k46' = 0.0003*(i468*OH_radical+i469*H2O2+i4610*DA_quinone+i4686*O2)
 
 Assignment Rule (name: k47_0) k47' = 0.0003*(i478*OH_radical+i479*H2O2+i4710*DA_quinone+i4786*O2)
 
 Assignment Rule (name: k48_0) k48' = 0.0003*(i488*OH_radical+i489*H2O2+i4810*DA_quinone+i4886*O2)
 
 Rate Rule (name: Fe2) d [ Fe2+] / d t= (J21-J20)+0.01
 
Functions (7)
 
 J3Sub lambda(K, X1, G1, X2, G2, X3, G3, K*X1^G1*X2^G2*X3^G3)
 
 J1Sub lambda(K, X, G, K*X^G)
 
 J2Sub lambda(K, X1, G1, X2, G2, K*X1^G1*X2^G2)
 
 J1Sub3Mod lambda(K, X1, G1, X2, G2, X3, G3, X4, G4, K*X1^G1*X2^G2*X3^G3*X4^G4)
 
 J2Sub1Mod lambda(K, X1, G1, X2, G2, X3, G3, K*X1^G1*X2^G2*X3^G3)
 
 J1Sub1Mod lambda(K, X1, G1, X2, G2, K*X1^G1*X2^G2)
 
 J3Sub1Mod lambda(K, X1, G1, X2, G2, X3, G3, X4, G4, K*X1^G1*X2^G2*X3^G3*X4^G4)
 
 Neuronal cytosol Spatial dimensions: 3.0  Compartment size: 1.0
 
 Protofibril
Compartment: Neuronal cytosol
Initial concentration: 0.05
 
 Fibril
Compartment: Neuronal cytosol
Initial concentration: 0.025
 
 Lewy_body
Compartment: Neuronal cytosol
Initial concentration: 0.01
 
 Dopamine
Compartment: Neuronal cytosol
Initial concentration: 2.0
 
 OH-
Compartment: Neuronal cytosol
Initial concentration: 0.5
 
 OH_radical
Compartment: Neuronal cytosol
Initial concentration: 0.02
 
 H2O2
Compartment: Neuronal cytosol
Initial concentration: 0.1
 
 DA_quinone
Compartment: Neuronal cytosol
Initial concentration: 0.05
 
 Ubiquitin
Compartment: Neuronal cytosol
Initial concentration: 1.0
 
 E1
Compartment: Neuronal cytosol
Initial concentration: 0.2
 
 Ub-E1
Compartment: Neuronal cytosol
Initial concentration: 0.35
 
 UbcH8
Compartment: Neuronal cytosol
Initial concentration: 0.2
 
 UbcH8-Ub
Compartment: Neuronal cytosol
Initial concentration: 0.35
 
 Parkin
Compartment: Neuronal cytosol
Initial concentration: 0.2
 
 Parkin-sub
Compartment: Neuronal cytosol
Initial concentration: 0.1
 
 Parkin-synphilin-1
Compartment: Neuronal cytosol
Initial concentration: 1.3
 
 Parkin-synphilin-1-ub
Compartment: Neuronal cytosol
Initial concentration: 2.5
 
 Parkin-sub-ub4
Compartment: Neuronal cytosol
Initial concentration: 0.2
 
 Fragments
Compartment: Neuronal cytosol
Initial concentration: 0.1
 
 UCH-L1
Compartment: Neuronal cytosol
Initial concentration: 0.5
 
 L-Dopa
Compartment: Neuronal cytosol
Initial concentration: 1.0
 
 DOPAL
Compartment: Neuronal cytosol
Initial concentration: 0.05
 
 DOPAC
Compartment: Neuronal cytosol
Initial concentration: 0.3
 
 GSH
Compartment: Neuronal cytosol
Initial concentration: 1.5
 
 GSSG
Compartment: Neuronal cytosol
Initial concentration: 1.5
 
 Fe2+
Compartment: Neuronal cytosol
Initial concentration: 0.5
 
 Fe3+
Compartment: Neuronal cytosol
Initial concentration: 0.5
 
 UbcH8ub2
Compartment: Neuronal cytosol
Initial concentration: 0.35
 
 UbcH8ub3
Compartment: Neuronal cytosol
Initial concentration: 0.35
 
 UbcH8ub4
Compartment: Neuronal cytosol
Initial concentration: 0.35
 
 UbcH13/Uev1a
Compartment: Neuronal cytosol
Initial concentration: 0.2
 
 UbcH13/Uev1a-ub
Compartment: Neuronal cytosol
Initial concentration: 0.35
 
 asyn-UCH-L1
Compartment: Neuronal cytosol
Initial concentration: 0.1
 
 asyn-ub
Compartment: Neuronal cytosol
Initial concentration: 0.05
 
 Protofibril-UCH-L1
Compartment: Neuronal cytosol
Initial concentration: 0.025
 
 Protofibril-Ub
Compartment: Neuronal cytosol
Initial concentration: 0.013
 
 UCH-L1-asyn-ub4
Compartment: Neuronal cytosol
Initial concentration: 0.1
 
 Hsc70-asyn
Compartment: Neuronal cytosol
Initial concentration: 0.1
 
 Hsc70-Protofibril
Compartment: Neuronal cytosol
Initial concentration: 0.025
 
 Hsc70-fibril
Compartment: Neuronal cytosol
Initial concentration: 0.013
 
 Hsc70
Compartment: Neuronal cytosol
Initial concentration: 0.5
 
 DA-S-parkin
Compartment: Neuronal cytosol
Initial concentration: 0.2
 
 O2-
Compartment: Neuronal cytosol
Initial concentration: 0.02
 
 DA-GSH
Compartment: Neuronal cytosol
Initial concentration: 0.2
 
 Neuromelanin
Compartment: Neuronal cytosol
Initial concentration: 1.0
 
 Neuromelanin-ntox-Fe3+
Compartment: Neuronal cytosol
Initial concentration: 0.5
 
 Alpha_synuclein
Compartment: Neuronal cytosol
Initial concentration: 0.2
Constant
 
 ATP
Compartment: Neuronal cytosol
Initial concentration: 2.0
Constant
 
 Synphilin-1
Compartment: Neuronal cytosol
Initial concentration: 0.05
Constant
 
 Substrate
Compartment: Neuronal cytosol
Initial concentration: 0.4
Constant
 
 TH
Compartment: Neuronal cytosol
Initial concentration: 0.6
Constant
 
 L-Tyr
Compartment: Neuronal cytosol
Initial concentration: 5.0
Constant
 
 CO2
Compartment: Neuronal cytosol
Initial concentration: 0.5
Constant
 
 Neurotoxins
Compartment: Neuronal cytosol
Initial concentration: 0.01
Constant
 
 Bioamines
Compartment: Neuronal cytosol
Initial concentration: 0.1
Constant
 
 VMAT2
Compartment: Neuronal cytosol
Initial concentration: 2.0
Constant
 
 O2
Compartment: Neuronal cytosol
Initial concentration: 2.0
Constant
 
 MAO
Compartment: Neuronal cytosol
Initial concentration: 1.5
Constant
 
 NH3
Compartment: Neuronal cytosol
Initial concentration: 0.5
Constant
 
 ALDH
Compartment: Neuronal cytosol
Initial concentration: 1.5
Constant
 
 NAD+
Compartment: Neuronal cytosol
Initial concentration: 1.5
Constant
 
 NADH
Compartment: Neuronal cytosol
Initial concentration: 1.5
Constant
 
 Catalase
Compartment: Neuronal cytosol
Initial concentration: 1.0
Constant
 
 H2O
Compartment: Neuronal cytosol
Initial concentration: 3.0
Constant
 
 Gluta_per
Compartment: Neuronal cytosol
Initial concentration: 0.8
Constant
 
 Gluta_red
Compartment: Neuronal cytosol
Initial concentration: 0.8
Constant
 
 DDC
Compartment: Neuronal cytosol
Initial concentration: 1.5
Constant
 
 Preautophagosome_membrane
Compartment: Neuronal cytosol
Initial concentration: 1.0
Constant
 
 SOD
Compartment: Neuronal cytosol
Initial concentration: 0.6
Constant
 
 Cysteine
Compartment: Neuronal cytosol
Initial concentration: 0.5
Constant
 
 Vesicle Spatial dimensions: 3.0  Compartment size: 1.0
 
 V-DA
Compartment: Vesicle
Initial concentration: 10.0
 
 V-ntox-ba
Compartment: Vesicle
Initial concentration: 0.3
 
 Vesicle
Compartment: Vesicle
Initial concentration: 1.0
Constant
 
 Autophagosome Spatial dimensions: 3.0  Compartment size: 1.0
 
 Autophagosome
Compartment: Autophagosome
Initial concentration: 0.5
 
 Proteasome Spatial dimensions: 3.0  Compartment size: 1.0
 
 Proteasome
Compartment: Proteasome
Initial concentration: 1.5
Constant
 
 Lysosome Spatial dimensions: 3.0  Compartment size: 1.0
 
 Lysosome
Compartment: Lysosome
Initial concentration: 2.5
Constant
 
Global Parameters (245)
 
   g11
Value: 1.0
Constant
 
   p186
Value: 0.5
Constant
 
   p110
Value: 1.0
Constant
 
   p19
Value: 1.0
Constant
 
   p18
Value: 1.0
Constant
 
 k1
Value: 0.03
Constant
 
   g22
Value: 1.0
Constant
 
   p286
Value: 0.25
Constant
 
   p210
Value: 0.5
Constant
 
   p29
Value: 0.5
Constant
 
   p28
Value: 0.5
Constant
 
   i26
Value: -1.0
Constant
 
   k2
Value: 0.01
Constant
 
   g326
Value: 1.0
Constant
 
   g23
Value: 1.0
Constant
 
   k3
Value: 0.007
Constant
 
 k4
Value: 0.9
Constant
 
   i41
Value: -0.01
Constant
 
   i42
Value: -0.01
Constant
 
   i43
Value: -0.01
Constant
 
   g412
Value: 1.0
Constant
 
   g415
Value: 1.0
Constant
 
   g427
Value: 1.0
Constant
 
   g430
Value: 1.0
Constant
 
   k6
Value: 0.5
Constant
 
   g613
Value: 1.0
Constant
 
   g614
Value: 1.0
Constant
 
   g615
Value: 1.0
Constant
 
   k7
Value: 0.03
Constant
 
   g715
Value: 1.0
Constant
 
   g716
Value: 1.0
Constant
 
   g717
Value: 1.0
Constant
 
   k8
Value: 0.001
Constant
 
   g819
Value: 1.0
Constant
 
   g821
Value: 1.0
Constant
 
   k9
Value: 0.001
Constant
 
   g919
Value: 1.0
Constant
 
   g920
Value: 1.0
Constant
 
   k10
Value: 0.05
Constant
 
   g1025
Value: 1.0
Constant
 
   g1072
Value: 1.0
Constant
 
   k11
Value: 0.05
Constant
 
   g1124
Value: 1.0
Constant
 
   g1170
Value: 1.0
Constant
 
   k13
Value: 0.1
Constant
 
   i131
Value: -0.01
Constant
 
   i1310
Value: -0.01
Constant
 
   g1335
Value: 1.0
Constant
 
   g1336
Value: 1.0
Constant
 
   g1351
Value: 1.0
Constant
 
   k14
Value: 3.0
Constant
 
   g1437
Value: 1.0
Constant
 
   g1467
Value: 1.0
Constant
 
   k15
Value: 0.2
Constant
 
   i152
Value: -0.1
Constant
 
   g156
Value: 1.0
Constant
 
   g1544
Value: 1.0
Constant
 
   g1545
Value: 1.0
Constant
 
   k16
Value: 1.0E-4
Constant
 
   g1643
Value: 1.0
Constant
 
   g1644
Value: 1.0
Constant
 
   k17
Value: 1.0E-4
Constant
 
   g1742
Value: 1.0
Constant
 
   g1744
Value: 1.0
Constant
 
   k18
Value: 0.02
Constant
 
   g186
Value: 1.0
Constant
 
   g1851
Value: 1.0
Constant
 
   k19
Value: 0.01
Constant
 
   g196
Value: 1.0
Constant
 
   g1951
Value: 1.0
Constant
 
   g1953
Value: 1.0
Constant
 
   g1960
Value: 1.0
Constant
 
   k20
Value: 0.1
Constant
 
   g209
Value: 1.0
Constant
 
   g2065
Value: 1.0
Constant
 
   k21
Value: 0.1
Constant
 
   g2166
Value: 1.0
Constant
 
   k22
Value: 0.5
Constant
 
   g229
Value: 1.0
Constant
 
   g2259
Value: 1.0
Constant
 
   k23
Value: 0.5
Constant
 
   g239
Value: 1.0
Constant
 
   g2361
Value: 1.0
Constant
 
   g2362
Value: 1.0
Constant
 
   k24
Value: 1.0
Constant
 
   g2463
Value: 1.0
Constant
 
   g2464
Value: 1.0
Constant
 
   k25
Value: 0.05
Constant
 
   g2552
Value: 1.0
Constant
 
   g2555
Value: 0.3
Constant
 
   g2556
Value: 0.25
Constant
 
   k26f
Value: 0.05
Constant
 
   g26f15
Value: 1.0
Constant
 
   g26f16
Value: 1.0
Constant
 
   g26f18
Value: 1.0
Constant
 
   k26r
Value: 0.005
Constant
 
   g26r30
Value: 1.0
Constant
 
   g26r68
Value: 1.0
Constant
 
   k27f
Value: 0.05
Constant
 
   g27f15
Value: 1.0
Constant
 
   g27f16
Value: 1.0
Constant
 
   g27f68
Value: 1.0
Constant
 
   k27r
Value: 0.005
Constant
 
   g27r30
Value: 1.0
Constant
 
   g27r69
Value: 1.0
Constant
 
   k28f
Value: 0.05
Constant
 
   g28f15
Value: 1.0
Constant
 
   g28f16
Value: 1.0
Constant
 
   g28f69
Value: 1.0
Constant
 
   k28r
Value: 0.005
Constant
 
   g28r30
Value: 1.0
Constant
 
   g28r70
Value: 1.0
Constant
 
   k29
Value: 0.05
Constant
 
   g2915
Value: 1.0
Constant
 
   g2916
Value: 1.0
Constant
 
   g2971
Value: 1.0
Constant
 
   k30
Value: 0.001
Constant
 
   g301
Value: 1.0
Constant
 
   g3030
Value: 1.0
Constant
 
   k31
Value: 0.05
Constant
 
   g3172
Value: 1.0
Constant
 
   g3173
Value: 1.0
Constant
 
   k32
Value: 0.001
Constant
 
   g321
Value: 1.0
Constant
 
   p328
Value: 0.1
Constant
 
   p329
Value: 0.1
Constant
 
   p3210
Value: 0.1
Constant
 
   p3286
Value: 0.05
Constant
 
   g3274
Value: 1.0
Constant
 
   k33
Value: 0.001
Constant
 
   g332
Value: 1.0
Constant
 
   g3330
Value: 1.0
Constant
 
   k34
Value: 0.05
Constant
 
   g3472
Value: 1.0
Constant
 
   g3475
Value: 1.0
Constant
 
   k35
Value: 0.001
Constant
 
   g352
Value: 1.0
Constant
 
   p358
Value: 0.1
Constant
 
   p359
Value: 0.1
Constant
 
   p3510
Value: 0.1
Constant
 
   p3586
Value: 0.05
Constant
 
   g3576
Value: 1.0
Constant
 
   k36
Value: 0.05
Constant
 
   i368
Value: -0.1
Constant
 
   i369
Value: -0.1
Constant
 
   i3610
Value: -0.1
Constant
 
   i3686
Value: -0.05
Constant
 
   g3677
Value: 1.0
Constant
 
   g3679
Value: 1.0
Constant
 
   k37
Value: 0.05
Constant
 
   g3770
Value: 1.0
Constant
 
   g3773
Value: 1.0
Constant
 
   k38
Value: 0.7
Constant
 
   i381
Value: -0.01
Constant
 
   i382
Value: -0.01
Constant
 
   i383
Value: -0.01
Constant
 
   g3812
Value: 1.0
Constant
 
   g3815
Value: 1.0
Constant
 
   g3830
Value: 1.0
Constant
 
   g3878
Value: 1.0
Constant
 
   k43
Value: 0.05
Constant
 
   g431
Value: 1.0
Constant
 
   g4384
Value: 1.0
Constant
 
   k44
Value: 0.045
Constant
 
   g442
Value: 1.0
Constant
 
   g4484
Value: 1.0
Constant
 
   k45
Value: 0.04
Constant
 
   g453
Value: 1.0
Constant
 
   g4584
Value: 1.0
Constant
 
   k46
Value: 0.03
Constant
 
   i468
Value: -0.1
Constant
 
   i469
Value: -0.1
Constant
 
   i4610
Value: -0.1
Constant
 
   i4686
Value: -0.05
Constant
 
   g4677
Value: 1.0
Constant
 
   g4681
Value: 1.0
Constant
 
 k47
Value: 0.03
Constant
 
   i478
Value: -0.1
Constant
 
   i479
Value: -0.1
Constant
 
   i4710
Value: -0.1
Constant
 
   i4786
Value: -0.05
Constant
 
   g4777
Value: 1.0
Constant
 
   g4782
Value: 1.0
Constant
 
   k48
Value: 0.03
Constant
 
   i488
Value: -0.1
Constant
 
   i489
Value: -0.1
Constant
 
   i4810
Value: -0.1
Constant
 
   i4886
Value: -0.05
Constant
 
   g4877
Value: 1.0
Constant
 
   g4883
Value: 1.0
Constant
 
   k50
Value: 0.05
Constant
 
   g501
Value: 1.0
Constant
 
   g5080
Value: 1.0
Constant
 
   k51
Value: 0.05
Constant
 
   g512
Value: 1.0
Constant
 
   g5180
Value: 1.0
Constant
 
   k52
Value: 0.05
Constant
 
   g523
Value: 1.0
Constant
 
   g5280
Value: 1.0
Constant
 
   k53
Value: 0.05
Constant
 
   g534
Value: 1.0
Constant
 
   g5380
Value: 1.0
Constant
 
   k54
Value: 0.005
Constant
 
   g5410
Value: 1.0
Constant
 
   g5419
Value: 1.0
Constant
 
   k55
Value: 0.05
Constant
 
   g556
Value: 1.0
Constant
 
   g5586
Value: 1.0
Constant
 
   k56
Value: 0.05
Constant
 
   g5686
Value: 1.0
Constant
 
   g5687
Value: 1.0
Constant
 
   k57
Value: 0.005
Constant
 
   g5710
Value: 1.0
Constant
 
   g5762
Value: 1.0
Constant
 
   k100
Value: 0.005
Constant
 
   g10037
Value: 1.0
Constant
 
   g10051
Value: 1.0
Constant
 
   g100115
Value: 1.0
Constant
 
   k101
Value: 0.005
Constant
 
   g10136
Value: 1.0
Constant
 
   g10151
Value: 1.0
Constant
 
   g101115
Value: 1.0
Constant
 
   k102
Value: 0.005
Constant
 
   g10210
Value: 1.0
Constant
 
   g10251
Value: 1.0
Constant
 
   g102115
Value: 1.0
Constant
 
   k115
Value: 0.5
Constant
 
   g11565
Value: 1.0
Constant
 
   g11566
Value: 1.0
Constant
 
   g115118
Value: 1.0
Constant
 
   k116
Value: 0.5
Constant
 
   g11642
Value: 1.0
Constant
 
   g116118
Value: 1.0
Constant
 
  k1'
Value: 5.4E-5
 
  k2'
Value: -1.91E-4
 
  k4'
Value: -2.475E-5
 
  k13'
Value: -2.5E-6
 
  k15'
Value: -1.0E-5
 
  k32'
Value: 1.8E-7
 
  k35'
Value: 1.8E-7
 
  k36'
Value: -9.0E-6
 
  k38'
Value: -1.925E-5
 
  k46'
Value: -5.4E-6
 
  k47'
Value: -5.4E-6
 
  k48'
Value: -5.4E-6
 
Representative curation result(s)
Representative curation result(s) of BIOMD0000000575

Curator's comment: (updated: 14 Apr 2015 12:09:56 GMT)

Figure 15 of the reference publication has been reproduced here. Dynamics of protofibrils, fibrils and Lewy bodies are plotted over 100 time units.
This figure displays a percentage comparison of a disease model, where levels of α-synuclein in the system are increased by 10%, and the baseline model. (i.e. α-synuclein increases to 0,22 at disease model).

For the sake of simulation, data from both models (disease and baseline) was merged. Subsequently, the disease model was divided by the baseline model and percentage format was applied.

The simulation was done using Copasi v4.14 (Build 89) and the plot was generated using Gnuplot. The Copasi file of the baseline model with simulation settings can be downloaded from the below link:

Additional file(s)
  • Sass2009 - Approach to an α-synuclein-based BST model of Parkinson's disease:
    Copasi file of the model
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