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BIOMD0000000293 - Proctor2010 - UCHL1 Protein Aggregation

 

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Reference Publication
Publication ID: 20949132
Proctor CJ, Tangeman PJ, Ardley HC.
Modelling the role of UCH-L1 on protein aggregation in age-related neurodegeneration.
PLoS ONE 2010; 5(10): e13175
Center for Integrated Systems Biology of Ageing and Nutrition, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, United Kingdom. c.j.proctor@ncl.ac.uk  [more]
Model
Original Model: Proctor_UCHL1_PD
Submitter: Carole Proctor
Submission ID: MODEL0912070000
Submission Date: 07 Dec 2009 13:19:38 UTC
Last Modification Date: 08 Apr 2016 17:54:30 UTC
Creation Date: 07 Jan 2011 12:33:39 UTC
Encoders:  Vijayalakshmi Chelliah
   Carole J Proctor
set #1
bqbiol:hasTaxon Taxonomy Homo sapiens
set #2
bqbiol:isPartOf KEGG Pathway Parkinson's disease
set #3
bqmodel:isDerivedFrom BioModels Database Proctor2007_ubiquitine
set #4
bqbiol:isVersionOf Gene Ontology inclusion body assembly
Gene Ontology thiol-dependent ubiquitin-specific protease activity
Gene Ontology negative regulation of proteasomal ubiquitin-dependent protein catabolic process
set #5
bqbiol:hasVersion Human Disease Ontology neurodegenerative disease
set #6
bqbiol:hasProperty Human Disease Ontology Parkinson's disease
Notes

This a model from the article:
Modelling the Role of UCH-L1 on Protein Aggregation in Age-Related Neurodegeneration.
Proctor CJ, Tangeman PJ, Ardley HC. PLoS One. 2010 Oct 6;5(10):e13175 20949132 ,
Abstract:
Overexpression of the de-ubiquitinating enzyme UCH-L1 leads to inclusion formation in response to proteasome impairment. These inclusions contain components of the ubiquitin-proteasome system and α-synuclein confirming that the ubiquitin-proteasome system plays an important role in protein aggregation. The processes involved are very complex and so we have chosen to take a systems biology approach to examine the system whereby we combine mathematical modelling with experiments in an iterative process. The experiments show that cells are very heterogeneous with respect to inclusion formation and so we use stochastic simulation. The model shows that the variability is partly due to stochastic effects but also depends on protein expression levels of UCH-L1 within cells. The model also indicates that the aggregation process can start even before any proteasome inhibition is present, but that proteasome inhibition greatly accelerates aggregation progression. This leads to less efficient protein degradation and hence more aggregation suggesting that there is a vicious cycle. However, proteasome inhibition may not necessarily be the initiating event. Our combined modelling and experimental approach show that stochastic effects play an important role in the aggregation process and could explain the variability in the age of disease onset. Furthermore, our model provides a valuable tool, as it can be easily modified and extended to incorporate new experimental data, test hypotheses and make testable predictions.


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.

In summary, you are entitled to use this encoded model in absolutely any manner you deem suitable, verbatim, or with modification, alone or embedded it in a larger context, redistribute it, commercially or not, in a restricted way or not.


To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.

Model
Publication ID: 20949132 Submission Date: 07 Dec 2009 13:19:38 UTC Last Modification Date: 08 Apr 2016 17:54:30 UTC Creation Date: 07 Jan 2011 12:33:39 UTC
Mathematical expressions
Reactions
UbSynthesis UbDegradation UbUpregulation ProteinSynthesis
Misfolding Refolding MisPE3Binding MisPE3Release
E1UbBinding E2UbBinding Monoubiquitination Polyubiquitination1
Polyubiquitination2 Polyubiquitination3 Polyubiquitination4 Polyubiquitination5
Polyubiquitination6 Polyubiquitination7 MisPDUBbinding1 MisPDUBbinding2
MisPDUBbinding3 MisPDUBbinding4 MisPDUBbinding5 MisPDUBbinding6
MisPDUBbinding7 MisPDUBbinding8 Deubiquitination8 Deubiquitination7
Deubiquitination6 Deubiquitination5 Deubiquitination4 Deubiquitination3
Deubiquitination2 Deubiquitination1 ProteasomeBindingUb4 ProteasomeBindingUb5
ProteasomeBindingUb6 ProteasomeBindingUb7 ProteasomeBindingUb8 DeubiquitinationBoundMisP5
DeubiquitinationBoundMisP4 DeubiquitinationBoundMisP3 DeubiquitinationBoundMisP2 DeubiquitinationBoundMisP1
ProteasomeActivity1 ProteasomeActivity2 ProteasomeActivity3 ProteasomeActivity4
ProteasomeActivity5 Aggregation1 Aggregation2 Aggregation3
Aggregation4 Aggregation5 Disaggregation1 Disaggregation2
Disaggregation3 Disaggregation4 Disaggregation5 InclusionFormation
InclusionGrowth1 InclusionGrowth2 InclusionGrowth3 InclusionGrowth4
InclusionGrowth5 InclusionGrowth6 InclusionGrowth7 InclusionGrowth8
InclusionGrowth9 InclusionGrowth10 InclusionGrowth11 InclusionGrowth12
InclusionGrowth13 InclusionGrowth14 InclusionGrowth15 InclusionGrowth16
InclusionGrowth17 InclusionGrowth18 ProteasomeInhibition1 ProteasomeInhibition2
ProteasomeInhibition3 ProteasomeInhibition4 ProteasomeInhibition5 ROSgenerationSmallAggP1
ROSgenerationSmallAggP2 ROSgenerationSmallAggP3 ROSgenerationSmallAggP4 ROSgenerationSmallAggP5
UCHL1Synthesis UCHL1ProteasomeBinding UCHL1ProteasomeDegradation UCHL1LysosomalDegradation
UCHL1damage UCHL1DamgedProteasomeBinding UCHL1DamagedProteasomeDegradation UCHL1DamagedLysosomalDegradation
UCHL1Lamp2abinding UCHL1Lamp2aRelease UbUCHL1binding UbUCHL1release
SUBsynthesis SUBmisfolding SUBRefolding E3SUBBinding
E3SUBRelease SUBMonoubiquitination SUBPolyubiquitination1 SUBPolyubiquitination2
SUBPolyubiquitination3 SUBPolyubiquitination4 SUBPolyubiquitination5 SUBPolyubiquitination6
SUBPolyubiquitination7 SUBUCHL1binding1 SUBUCHL1binding2 SUBUCHL1binding3
SUBUCHL1binding4 SUBUCHL1binding5Ub_UCHL1 SUBUCHL1binding6 SUBUCHL1binding7
SUBUCHL1binding8 SUBDeubiquitination8 SUBDeubiquitination7 SUBDeubiquitination6
SUBDeubiquitination5 SUBDeubiquitination4 SUBDeubiquitination3 SUBDeubiquitination2
SUBDeubiquitination1 SUBProteasomeBindingUb4 SUBProteasomeBindingUb5 SUBProteasomeBindingUb6
SUBProteasomeBindingUb7 SUBProteasomeBindingUb8 DeubiquitinationBoundSUB8 DeubiquitinationBoundSUB7
DeubiquitinationBoundSUB6 DeubiquitinationBoundSUB5 DeubiquitinationBoundSUB4 SUBDegradationUb4
SUBDegradationUb5 SUBDegradationUb6 SUBDegradationUb7 SUBDegradationUb8
asynSynthesis1 asynProt20Sbinding asynProt20Sdegradation asynLamp2aBinding
asynCMAdegradation asynDamage asyn_damParkinBinding asyn_damParkinRelease
AsynMonoubiquitination AsynPolyubiquitination1 AsynPolyubiquitination2 AsynPolyubiquitination3
AsynPolyubiquitination4 AsynPolyubiquitination5 AsynPolyubiquitination6 AsynPolyubiquitination7
AsynDUBbindingUb8 AsynDUBbindingUb7 AsynDUBbindingUb6 AsynDUBbindingUb5
AsynDUBbindingUb4 AsynDUBbindingUb3 AsynDUBbindingUb2 AsynDUBbindingUb1
AsynDeubiquitinationUb8 AsynDeubiquitinationUb7 AsynDeubiquitinationUb6 AsynDeubiquitinationUb5
AsynDeubiquitinationUb4 AsynDeubiquitinationUb3 AsynDeubiquitinationUb2 AsynDeubiquitinationUb1
AsynProteasomeBindingUb4 AsynProteasomeBindingUb5 AsynProteasomeBindingUb6 AsynProteasomeBindingUb7
AsynProteasomeBindingUb8 DeubiquitinationBoundasyn_damUb8 DeubiquitinationBoundasynDamUb7 DeubiquitinationBoundasynDamUb6
DeubiquitinationBoundasynDamUb5 DeubiquitinationBoundasynDamUb4 AsynProteasomeActivityUb4 AsynDegradationUb5
AsynDegradationUb6 AsynDegradationUb7 AsynDegradationUb8 Aggregationasyn1
Aggregationasyn2 Aggregationasyn3 Aggregationasyn4 Aggregationasyn5
DisAggregationasyn1 DisAggregationasyn2 DisAggregationasyn3 DisAggregationasyn4
DisAggregationasyn5 AggA1ProteasomeInhibition AggA2ProteasomeInhibition AggA3ProteasomeInhibition
AggA4ProteasomeInhibition AggA5ProteasomeInhibition AsynInclusionFormation AsynInclusionGrowth
ROSgenerationSmallAggA1 ROSgenerationSmallAggA2 ROSgenerationSmallAggA3 ROSgenerationSmallAggA4
ROSgenerationSmallAggA5 AggregationAsynDam1 AggregationAsynDam2 AggregationAsynDam3
AggregationAsynDam4 AggregationAsynDam5 DisaggregationAsynDam1 DisaggregationAsynDam2
DisaggregationAsynDam3 DisaggregationAsynDam4 DisaggregationAsynDam5 AggD1ProteasomeInhibition
AggD2ProteasomeInhibition AggD3ProteasomeInhibition AggD4ProteasomeInhibition AggD5ProteasomeInhibition
AsynDamInclusionFormation AsynDamInclusionGrowth1 AsynDamInclusionGrowth2 AsynDamInclusionGrowth3
AsynDamInclusionGrowth4 AsynDamInclusionGrowth5 AsynDamInclusionGrowth6 AsynDamInclusionGrowth7
AsynDamInclusionGrowth8 AsynDamInclusionGrowth9 AsynDamInclusionGrowth10 AsynDamInclusionGrowth11
AsynDamInclusionGrowth12 AsynDamInclusionGrowth13 AsynDamInclusionGrowth14 AsynDamInclusionGrowth15
AsynDamInclusionGrowth16 AsynDamInclusionGrowth17 AsynDamInclusionGrowth18 ROSgenerationSmallAggD1
ROSgenerationSmallAggD2 ROSgenerationSmallAggD3 ROSgenerationSmallAggD4 ROSgenerationSmallAggD5
AggregationUCHL1Dam1 AggregationUCHL1Dam2 AggregationUCHL1Dam3 AggregationUCHL1Dam4
AggregationUCHL1Dam5 DisaggregationUCHL1Dam1 DisaggregationUCHL1Dam2 DisaggregationUCHL1Dam3
DisaggregationUCHL1Dam4 DisaggregationUCHL1Dam5 AggU1ProteasomeInhibition AggU2ProteasomeInhibition
AggU3ProteasomeInhibition AggU4ProteasomeInhibition AggU5ProteasomeInhibition UCHL1DamInclusionFormation
UCHL1DamagedSequestering UCHL1DamagedLamp2aSequestering ROSgenerationSmallAggU1 ROSgenerationSmallAggU2
ROSgenerationSmallAggU3 ROSgenerationSmallAggU4 ROSgenerationSmallAggU5 SUBAggregation1
SUBAggregation2 SUBAggregation3 SUBAggregation4 SUBAggregation5
SUBDisaggregation1 SUBDisaggregation2 SUBDisaggregation3 SUBDisaggregation4
SUBDisaggregation5 AggS1ProteasomeInhibition AggS2ProteasomeInhibition AggS3ProteasomeInhibition
AggS4ProteasomeInhibition AggS5ProteasomeInhibition SUBInclusionFormation SUBInclusionGrowth0
SUBInclusionGrowth1 SUBInclusionGrowth2 SUBInclusionGrowth3 SUBInclusionGrowth4
SUBInclusionGrowth5 SUBInclusionGrowth6 SUBInclusionGrowth7 SUBInclusionGrowth8
SUBInclusionGrowth9 SUBInclusionGrowth10 SUBInclusionGrowth11 SUBInclusionGrowth12
SUBInclusionGrowth13 SUBInclusionGrowth14 SUBInclusionGrowth15 SUBInclusionGrowth16
SUBInclusionGrowth17 ROSgenerationSmallAggS1 ROSgenerationSmallAggS2 ROSgenerationSmallAggS3
ROSgenerationSmallAggS4 ROSgenerationSmallAggS5 radicalFormation radicalScavenging
Rules
Assignment Rule (variable: Tot_MisP) Assignment Rule (variable: Tot_Protein) Assignment Rule (variable: Ub_Conjugates) Assignment Rule (variable: Tot_Ub)
Assignment Rule (variable: AggP) Assignment Rule (variable: Tot_asyn_dam) Assignment Rule (variable: Tot_asyn) Assignment Rule (variable: UCHL1_substrate)
Assignment Rule (variable: Tot_UCHL1)      
Physical entities
Compartments Species
cytosol NatP MisP Ub
E1 E2 E3
E3_MisP DUB Proteasome
ROS E1_Ub E2_Ub
E3_MisP_Ub E3_MisP_Ub2 E3_MisP_Ub3
E3_MisP_Ub4 E3_MisP_Ub5 E3_MisP_Ub6
E3_MisP_Ub7 E3_MisP_Ub8 MisP_Ub4_Proteasome
MisP_Ub5_Proteasome MisP_Ub6_Proteasome MisP_Ub7_Proteasome
MisP_Ub8_Proteasome E3_MisP_Ub_DUB E3_MisP_Ub2_DUB
E3_MisP_Ub3_DUB E3_MisP_Ub4_DUB E3_MisP_Ub5_DUB
E3_MisP_Ub6_DUB E3_MisP_Ub7_DUB E3_MisP_Ub8_DUB
AggP1 AggP2 AggP3
AggP4 AggP5 SeqAggP
AggP_Proteasome ATP ADP
AMP UCHL1 UCHL1_Proteasome
UCHL1_damaged_Proteasome Lysosome UCHL1_damaged
Lamp2a Lamp2a_UCHL1_damaged Ub_UCHL1
SUB SUB_misfolded E3SUB
E3SUB_SUB_misfolded E3SUB_SUB_misfolded_Ub E3SUB_SUB_misfolded_Ub2
E3SUB_SUB_misfolded_Ub3 E3SUB_SUB_misfolded_Ub4 E3SUB_SUB_misfolded_Ub5
E3SUB_SUB_misfolded_Ub6 E3SUB_SUB_misfolded_Ub7 E3SUB_SUB_misfolded_Ub8
E3SUB_SUB_misfolded_Ub_UCHL1 E3SUB_SUB_misfolded_Ub2_UCHL1 E3SUB_SUB_misfolded_Ub3_UCHL1
E3SUB_SUB_misfolded_Ub4_UCHL1 E3SUB_SUB_misfolded_Ub5_UCHL1 E3SUB_SUB_misfolded_Ub6_UCHL1
E3SUB_SUB_misfolded_Ub7_UCHL1 E3SUB_SUB_misfolded_Ub8_UCHL1 SUB_misfolded_Ub4_Proteasome
SUB_misfolded_Ub5_Proteasome SUB_misfolded_Ub6_Proteasome SUB_misfolded_Ub7_Proteasome
SUB_misfolded_Ub8_Proteasome asyn asyn_Proteasome
asyn_Lamp2a asyn_dam Parkin
Parkin_asyn_dam Parkin_asyn_dam_Ub Parkin_asyn_dam_Ub2
Parkin_asyn_dam_Ub3 Parkin_asyn_dam_Ub4 Parkin_asyn_dam_Ub5
Parkin_asyn_dam_Ub6 Parkin_asyn_dam_Ub7 Parkin_asyn_dam_Ub8
Parkin_asyn_dam_Ub_DUB Parkin_asyn_dam_Ub2_DUB Parkin_asyn_dam_Ub3_DUB
Parkin_asyn_dam_Ub4_DUB Parkin_asyn_dam_Ub5_DUB Parkin_asyn_dam_Ub6_DUB
Parkin_asyn_dam_Ub7_DUB Parkin_asyn_dam_Ub8_DUB asyn_dam_Ub4_Proteasome
asyn_dam_Ub5_Proteasome asyn_dam_Ub6_Proteasome asyn_dam_Ub7_Proteasome
asyn_dam_Ub8_Proteasome AggA1 AggA2
AggA3 AggA4 AggA5
AggD1 AggD2 AggD3
AggD4 AggD5 AggU1
AggU2 AggU3 AggU4
AggU5 AggS1 AggS2
AggS3 AggS4 AggS5
Source Sink aggasyn
aggasyndam aggParkin aggUb
aggE3 aggDUB aggMisP
aggUchl1 aggUchl1dam aggSUB
upregUb    
Global parameters
ksynNatP kmisfold krefold kbinMisPE3
krelMisPE3 kbinE1Ub kbinE2Ub kmonoUb
kpolyUb kactDUB kbinProt kactDUBProt
kactProt kagg1 kagg2 kdisagg1
kdisagg2 kdisagg3 kdisagg4 kdisagg5
kigrowth1 kigrowth2 kbinAggProt kbinMisPDUB
kgenROS kremROS kubs kubd
kubss ksynUCHL1 kbinUCHL1Prot kdegProtUCHL1
kdegLysUCHL1 kdamUCHL1 kbinLamp2aUCHL1dam krelLamp2aUCHL1dam
kdegLysUCHL1dam kbinUbUCHL1 krelUbUCHL1 kactUchl1
kbinSUBUCHL1 ksynSUB kmisfoldSUB krefoldSUB
kbinE3SUB krelE3SUB ksynasyn kbinasynProt
kdegasynProt kbinasynLamp2a kCMAasyn kdamasyn
kbinasynDUB kbinasynParkin krelasynParkin kaggasyn1
kaggasyn2 kdisaggasyn1 kdisaggasyn2 kdisaggasyn3
kdisaggasyn4 kdisaggasyn5 kgenROSAggP kagg1dam
kagg2dam kdisaggasyndam1 kdisaggasyndam2 kdisaggasyndam3
kdisaggasyndam4 kdisaggasyndam5 kdisagguchl1dam1 kdisagguchl1dam2
kdisagguchl1dam3 kdisagguchl1dam4 kdisagguchl1dam5 kaggSUB1
kaggSUB2 kdisaggSUB1 kdisaggSUB2 kdisaggSUB3
kdisaggSUB4 kdisaggSUB5 kproteff Tot_MisP
Tot_Protein Ub_Conjugates Tot_Ub AggP
Tot_asyn_dam Tot_asyn Tot_UCHL1 UCHL1_substrate
Reactions (316)
 
 UbSynthesis [Source] → [Ub];  
 
 UbDegradation [Ub] + [Proteasome] → [Proteasome];  
 
 UbUpregulation [MisP] → [MisP] + 3.0 × [Ub] + 3.0 × [upregUb];  
 
 ProteinSynthesis [Source] → [NatP];  
 
 Misfolding [NatP] + [ROS] → [MisP] + [ROS];  
 
 Refolding [MisP] → [NatP];  
 
 MisPE3Binding [MisP] + [E3] → [E3_MisP];  
 
 MisPE3Release [E3_MisP] → [MisP] + [E3];  
 
 E1UbBinding [E1] + [Ub] + [ATP] → [E1_Ub] + [AMP];  
 
 E2UbBinding [E2] + [E1_Ub] → [E2_Ub] + [E1];  
 
 Monoubiquitination [E2_Ub] + [E3_MisP] → [E3_MisP_Ub] + [E2];  
 
 Polyubiquitination1 [E3_MisP_Ub] + [E2_Ub] → [E3_MisP_Ub2] + [E2];  
 
 Polyubiquitination2 [E3_MisP_Ub2] + [E2_Ub] → [E3_MisP_Ub3] + [E2];  
 
 Polyubiquitination3 [E3_MisP_Ub3] + [E2_Ub] → [E3_MisP_Ub4] + [E2];  
 
 Polyubiquitination4 [E3_MisP_Ub4] + [E2_Ub] → [E3_MisP_Ub5] + [E2];  
 
 Polyubiquitination5 [E3_MisP_Ub5] + [E2_Ub] → [E3_MisP_Ub6] + [E2];  
 
 Polyubiquitination6 [E3_MisP_Ub6] + [E2_Ub] → [E3_MisP_Ub7] + [E2];  
 
 Polyubiquitination7 [E3_MisP_Ub7] + [E2_Ub] → [E3_MisP_Ub8] + [E2];  
 
 MisPDUBbinding1 [E3_MisP_Ub] + [DUB] → [E3_MisP_Ub_DUB];  
 
 MisPDUBbinding2 [E3_MisP_Ub2] + [DUB] → [E3_MisP_Ub2_DUB];  
 
 MisPDUBbinding3 [E3_MisP_Ub3] + [DUB] → [E3_MisP_Ub3_DUB];  
 
 MisPDUBbinding4 [E3_MisP_Ub4] + [DUB] → [E3_MisP_Ub4_DUB];  
 
 MisPDUBbinding5 [E3_MisP_Ub5] + [DUB] → [E3_MisP_Ub5_DUB];  
 
 MisPDUBbinding6 [E3_MisP_Ub6] + [DUB] → [E3_MisP_Ub6_DUB];  
 
 MisPDUBbinding7 [E3_MisP_Ub7] + [DUB] → [E3_MisP_Ub7_DUB];  
 
 MisPDUBbinding8 [E3_MisP_Ub8] + [DUB] → [E3_MisP_Ub8_DUB];  
 
 Deubiquitination8 [E3_MisP_Ub8_DUB] → [E3_MisP_Ub7_DUB] + [Ub];  
 
 Deubiquitination7 [E3_MisP_Ub7_DUB] → [E3_MisP_Ub6_DUB] + [Ub];  
 
 Deubiquitination6 [E3_MisP_Ub6_DUB] → [E3_MisP_Ub5_DUB] + [Ub];  
 
 Deubiquitination5 [E3_MisP_Ub5_DUB] → [E3_MisP_Ub4_DUB] + [Ub];  
 
 Deubiquitination4 [E3_MisP_Ub4_DUB] → [E3_MisP_Ub3_DUB] + [Ub];  
 
 Deubiquitination3 [E3_MisP_Ub3_DUB] → [E3_MisP_Ub2_DUB] + [Ub];  
 
 Deubiquitination2 [E3_MisP_Ub2_DUB] → [E3_MisP_Ub_DUB] + [Ub];  
 
 Deubiquitination1 [E3_MisP_Ub_DUB] → [E3_MisP] + [DUB] + [Ub];  
 
 ProteasomeBindingUb4 [E3_MisP_Ub4] + [Proteasome] → [E3] + [MisP_Ub4_Proteasome];  
 
 ProteasomeBindingUb5 [E3_MisP_Ub5] + [Proteasome] → [E3] + [MisP_Ub5_Proteasome];  
 
 ProteasomeBindingUb6 [E3_MisP_Ub6] + [Proteasome] → [E3] + [MisP_Ub6_Proteasome];  
 
 ProteasomeBindingUb7 [E3_MisP_Ub7] + [Proteasome] → [E3] + [MisP_Ub7_Proteasome];  
 
 ProteasomeBindingUb8 [E3_MisP_Ub8] + [Proteasome] → [E3] + [MisP_Ub8_Proteasome];  
 
 DeubiquitinationBoundMisP5 [MisP_Ub8_Proteasome] + [DUB] → [MisP_Ub7_Proteasome] + [Ub] + [DUB];  
 
 DeubiquitinationBoundMisP4 [MisP_Ub7_Proteasome] + [DUB] → [MisP_Ub6_Proteasome] + [Ub] + [DUB];  
 
 DeubiquitinationBoundMisP3 [MisP_Ub6_Proteasome] + [DUB] → [MisP_Ub5_Proteasome] + [Ub] + [DUB];  
 
 DeubiquitinationBoundMisP2 [MisP_Ub5_Proteasome] + [DUB] → [MisP_Ub4_Proteasome] + [Ub] + [DUB];  
 
 DeubiquitinationBoundMisP1 [MisP_Ub4_Proteasome] + [DUB] → [MisP] + [Proteasome] + 4.0 × [Ub] + [DUB];  
 
 ProteasomeActivity1 [MisP_Ub4_Proteasome] + [ATP] → 4.0 × [Ub] + [Proteasome] + [ADP];  
 
 ProteasomeActivity2 [MisP_Ub5_Proteasome] + [ATP] → 5.0 × [Ub] + [Proteasome] + [ADP];  
 
 ProteasomeActivity3 [MisP_Ub6_Proteasome] + [ATP] → 6.0 × [Ub] + [Proteasome] + [ADP];  
 
 ProteasomeActivity4 [MisP_Ub7_Proteasome] + [ATP] → 7.0 × [Ub] + [Proteasome] + [ADP];  
 
 ProteasomeActivity5 [MisP_Ub8_Proteasome] + [ATP] → 8.0 × [Ub] + [Proteasome] + [ADP];  
 
 Aggregation1 2.0 × [MisP] → [AggP1];  
 
 Aggregation2 [MisP] + [AggP1] → [AggP2];  
 
 Aggregation3 [MisP] + [AggP2] → [AggP3];  
 
 Aggregation4 [MisP] + [AggP3] → [AggP4];  
 
 Aggregation5 [MisP] + [AggP4] → [AggP5];  
 
 Disaggregation1 [AggP5] → [AggP4] + [MisP];  
 
 Disaggregation2 [AggP4] → [AggP3] + [MisP];  
 
 Disaggregation3 [AggP3] → [AggP2] + [MisP];  
 
 Disaggregation4 [AggP2] → [AggP1] + [MisP];  
 
 Disaggregation5 [AggP1] → 2.0 × [MisP];  
 
 InclusionFormation [MisP] + [AggP5] → [SeqAggP] + 7.0 × [aggMisP];  
 
 InclusionGrowth1 [MisP] + [SeqAggP] → 2.0 × [SeqAggP] + [aggMisP];  
 
 InclusionGrowth2 [E3_MisP] + [SeqAggP] → 2.0 × [SeqAggP] + [aggMisP] + [aggE3];  
 
 InclusionGrowth3 [E3_MisP_Ub] + [SeqAggP] → 2.0 × [SeqAggP] + [aggMisP] + [aggUb] + [aggE3];  
 
 InclusionGrowth4 [E3_MisP_Ub2] + [SeqAggP] → 2.0 × [SeqAggP] + [aggMisP] + 2.0 × [aggUb] + [aggE3];  
 
 InclusionGrowth5 [E3_MisP_Ub3] + [SeqAggP] → 2.0 × [SeqAggP] + [aggMisP] + 3.0 × [aggUb] + [aggE3];  
 
 InclusionGrowth6 [E3_MisP_Ub4] + [SeqAggP] → 2.0 × [SeqAggP] + [aggMisP] + 4.0 × [aggUb] + [aggE3];  
 
 InclusionGrowth7 [E3_MisP_Ub5] + [SeqAggP] → 2.0 × [SeqAggP] + [aggMisP] + 5.0 × [aggUb] + [aggE3];  
 
 InclusionGrowth8 [E3_MisP_Ub6] + [SeqAggP] → 2.0 × [SeqAggP] + [aggMisP] + 6.0 × [aggUb] + [aggE3];  
 
 InclusionGrowth9 [E3_MisP_Ub7] + [SeqAggP] → 2.0 × [SeqAggP] + [aggMisP] + 7.0 × [aggUb] + [aggE3];  
 
 InclusionGrowth10 [E3_MisP_Ub8] + [SeqAggP] → 2.0 × [SeqAggP] + 8.0 × [aggUb] + [aggE3];  
 
 InclusionGrowth11 [E3_MisP_Ub_DUB] + [SeqAggP] → 2.0 × [SeqAggP] + [aggMisP] + [aggUb] + [aggE3] + [aggDUB];  
 
 InclusionGrowth12 [E3_MisP_Ub2_DUB] + [SeqAggP] → 2.0 × [SeqAggP] + [aggMisP] + 2.0 × [aggUb] + [aggE3] + [aggDUB];  
 
 InclusionGrowth13 [E3_MisP_Ub3_DUB] + [SeqAggP] → 2.0 × [SeqAggP] + [aggMisP] + 3.0 × [aggUb] + [aggE3] + [aggDUB];  
 
 InclusionGrowth14 [E3_MisP_Ub4_DUB] + [SeqAggP] → 2.0 × [SeqAggP] + [aggMisP] + 4.0 × [aggUb] + [aggE3] + [aggDUB];  
 
 InclusionGrowth15 [E3_MisP_Ub5_DUB] + [SeqAggP] → 2.0 × [SeqAggP] + [aggMisP] + 5.0 × [aggUb] + [aggE3] + [aggDUB];  
 
 InclusionGrowth16 [E3_MisP_Ub6_DUB] + [SeqAggP] → 2.0 × [SeqAggP] + [aggMisP] + 6.0 × [aggUb] + [aggE3] + [aggDUB];  
 
 InclusionGrowth17 [E3_MisP_Ub7_DUB] + [SeqAggP] → 2.0 × [SeqAggP] + [aggMisP] + 7.0 × [aggUb] + [aggE3] + [aggDUB];  
 
 InclusionGrowth18 [E3_MisP_Ub8_DUB] + [SeqAggP] → 2.0 × [SeqAggP] + [aggMisP] + 8.0 × [aggUb] + [aggE3] + [aggDUB];  
 
 ProteasomeInhibition1 [AggP1] + [Proteasome] → [AggP_Proteasome];  
 
 ProteasomeInhibition2 [AggP2] + [Proteasome] → [AggP_Proteasome];  
 
 ProteasomeInhibition3 [AggP3] + [Proteasome] → [AggP_Proteasome];  
 
 ProteasomeInhibition4 [AggP4] + [Proteasome] → [AggP_Proteasome];  
 
 ProteasomeInhibition5 [AggP5] + [Proteasome] → [AggP_Proteasome];  
 
 ROSgenerationSmallAggP1 [AggP1] → [AggP1] + [ROS];  
 
 ROSgenerationSmallAggP2 [AggP2] → [AggP2] + [ROS];  
 
 ROSgenerationSmallAggP3 [AggP3] → [AggP3] + [ROS];  
 
 ROSgenerationSmallAggP4 [AggP4] → [AggP4] + [ROS];  
 
 ROSgenerationSmallAggP5 [AggP5] → [AggP5] + [ROS];  
 
 UCHL1Synthesis [Source] → [UCHL1];  
 
 UCHL1ProteasomeBinding [UCHL1] + [Proteasome] → [UCHL1_Proteasome];  
 
 UCHL1ProteasomeDegradation [UCHL1_Proteasome] → [Proteasome];  
 
 UCHL1LysosomalDegradation [UCHL1] + [Lysosome] → [Lysosome];  
 
 UCHL1damage [UCHL1] + [ROS] → [UCHL1_damaged] + [ROS];  
 
 UCHL1DamgedProteasomeBinding [UCHL1_damaged] + [Proteasome] → [UCHL1_damaged_Proteasome];  
 
 UCHL1DamagedProteasomeDegradation [UCHL1_damaged_Proteasome] → [Proteasome];  
 
 UCHL1DamagedLysosomalDegradation [UCHL1_damaged] + [Lysosome] → [Lysosome];  
 
 UCHL1Lamp2abinding [UCHL1_damaged] + [Lamp2a] → [Lamp2a_UCHL1_damaged];  
 
 UCHL1Lamp2aRelease [Lamp2a_UCHL1_damaged] → [UCHL1_damaged] + [Lamp2a];  
 
 UbUCHL1binding [Ub] + [UCHL1] → [Ub_UCHL1];  
 
 UbUCHL1release [Ub_UCHL1] → [Ub] + [UCHL1];  
 
 SUBsynthesis [Source] → [SUB];  
 
 SUBmisfolding [SUB] + [ROS] → [SUB_misfolded] + [ROS];  
 
 SUBRefolding [SUB_misfolded] → [SUB];  
 
 E3SUBBinding [SUB_misfolded] + [E3SUB] → [E3SUB_SUB_misfolded];  
 
 E3SUBRelease [E3SUB_SUB_misfolded] → [SUB_misfolded] + [E3SUB];  
 
 SUBMonoubiquitination [E2_Ub] + [E3SUB_SUB_misfolded] → [E3SUB_SUB_misfolded_Ub] + [E2];  
 
 SUBPolyubiquitination1 [E3SUB_SUB_misfolded_Ub] + [E2_Ub] → [E3SUB_SUB_misfolded_Ub2] + [E2];  
 
 SUBPolyubiquitination2 [E3SUB_SUB_misfolded_Ub2] + [E2_Ub] → [E3SUB_SUB_misfolded_Ub3] + [E2];  
 
 SUBPolyubiquitination3 [E3SUB_SUB_misfolded_Ub3] + [E2_Ub] → [E3SUB_SUB_misfolded_Ub4] + [E2];  
 
 SUBPolyubiquitination4 [E3SUB_SUB_misfolded_Ub4] + [E2_Ub] → [E3SUB_SUB_misfolded_Ub5] + [E2];  
 
 SUBPolyubiquitination5 [E3SUB_SUB_misfolded_Ub5] + [E2_Ub] → [E3SUB_SUB_misfolded_Ub6] + [E2];  
 
 SUBPolyubiquitination6 [E3SUB_SUB_misfolded_Ub6] + [E2_Ub] → [E3SUB_SUB_misfolded_Ub7] + [E2];  
 
 SUBPolyubiquitination7 [E3SUB_SUB_misfolded_Ub7] + [E2_Ub] → [E3SUB_SUB_misfolded_Ub8] + [E2];  
 
 SUBUCHL1binding1 [E3SUB_SUB_misfolded_Ub] + [UCHL1] → [E3SUB_SUB_misfolded_Ub_UCHL1];  
 
 SUBUCHL1binding2 [E3SUB_SUB_misfolded_Ub2] + [UCHL1] → [E3SUB_SUB_misfolded_Ub2_UCHL1];  
 
 SUBUCHL1binding3 [E3SUB_SUB_misfolded_Ub3] + [UCHL1] → [E3SUB_SUB_misfolded_Ub3_UCHL1];  
 
 SUBUCHL1binding4 [E3SUB_SUB_misfolded_Ub4] + [UCHL1] → [E3SUB_SUB_misfolded_Ub4_UCHL1];  
 
 SUBUCHL1binding5Ub_UCHL1 [E3SUB_SUB_misfolded_Ub5] + [UCHL1] → [E3SUB_SUB_misfolded_Ub5_UCHL1];  
 
 SUBUCHL1binding6 [E3SUB_SUB_misfolded_Ub6] + [UCHL1] → [E3SUB_SUB_misfolded_Ub6_UCHL1];  
 
 SUBUCHL1binding7 [E3SUB_SUB_misfolded_Ub7] + [UCHL1] → [E3SUB_SUB_misfolded_Ub7_UCHL1];  
 
 SUBUCHL1binding8 [E3SUB_SUB_misfolded_Ub8] + [UCHL1] → [E3SUB_SUB_misfolded_Ub8_UCHL1];  
 
 SUBDeubiquitination8 [E3SUB_SUB_misfolded_Ub8_UCHL1] → [E3SUB_SUB_misfolded_Ub7_UCHL1] + [Ub];  
 
 SUBDeubiquitination7 [E3SUB_SUB_misfolded_Ub7_UCHL1] → [E3SUB_SUB_misfolded_Ub6_UCHL1] + [Ub];  
 
 SUBDeubiquitination6 [E3SUB_SUB_misfolded_Ub6_UCHL1] → [E3SUB_SUB_misfolded_Ub5_UCHL1] + [Ub];  
 
 SUBDeubiquitination5 [E3SUB_SUB_misfolded_Ub5_UCHL1] → [E3SUB_SUB_misfolded_Ub4_UCHL1] + [Ub];  
 
 SUBDeubiquitination4 [E3SUB_SUB_misfolded_Ub4_UCHL1] → [E3SUB_SUB_misfolded_Ub3_UCHL1] + [Ub];  
 
 SUBDeubiquitination3 [E3SUB_SUB_misfolded_Ub3_UCHL1] → [E3SUB_SUB_misfolded_Ub2_UCHL1] + [Ub];  
 
 SUBDeubiquitination2 [E3SUB_SUB_misfolded_Ub2_UCHL1] → [E3SUB_SUB_misfolded_Ub_UCHL1] + [Ub];  
 
 SUBDeubiquitination1 [E3SUB_SUB_misfolded_Ub_UCHL1] → [E3SUB_SUB_misfolded] + [UCHL1] + [Ub];  
 
 SUBProteasomeBindingUb4 [E3SUB_SUB_misfolded_Ub4] + [Proteasome] → [SUB_misfolded_Ub4_Proteasome] + [E3SUB];  
 
 SUBProteasomeBindingUb5 [E3SUB_SUB_misfolded_Ub5] + [Proteasome] → [SUB_misfolded_Ub5_Proteasome] + [E3SUB];  
 
 SUBProteasomeBindingUb6 [E3SUB_SUB_misfolded_Ub6] + [Proteasome] → [SUB_misfolded_Ub6_Proteasome] + [E3SUB];  
 
 SUBProteasomeBindingUb7 [E3SUB_SUB_misfolded_Ub7] + [Proteasome] → [SUB_misfolded_Ub7_Proteasome] + [E3SUB];  
 
 SUBProteasomeBindingUb8 [E3SUB_SUB_misfolded_Ub8] + [Proteasome] → [SUB_misfolded_Ub8_Proteasome] + [E3SUB];  
 
 DeubiquitinationBoundSUB8 [SUB_misfolded_Ub8_Proteasome] + [DUB] → [SUB_misfolded_Ub7_Proteasome] + [Ub] + [DUB];  
 
 DeubiquitinationBoundSUB7 [SUB_misfolded_Ub7_Proteasome] + [DUB] → [SUB_misfolded_Ub6_Proteasome] + [Ub] + [DUB];  
 
 DeubiquitinationBoundSUB6 [SUB_misfolded_Ub6_Proteasome] + [DUB] → [SUB_misfolded_Ub5_Proteasome] + [Ub] + [DUB];  
 
 DeubiquitinationBoundSUB5 [SUB_misfolded_Ub5_Proteasome] + [DUB] → [SUB_misfolded_Ub4_Proteasome] + [Ub] + [DUB];  
 
 DeubiquitinationBoundSUB4 [SUB_misfolded_Ub4_Proteasome] + [DUB] → [SUB_misfolded] + [Proteasome] + 4.0 × [Ub] + [DUB];  
 
 SUBDegradationUb4 [SUB_misfolded_Ub4_Proteasome] + [ATP] → 4.0 × [Ub] + [Proteasome] + [ADP];  
 
 SUBDegradationUb5 [SUB_misfolded_Ub5_Proteasome] + [ATP] → 5.0 × [Ub] + [Proteasome] + [ADP];  
 
 SUBDegradationUb6 [SUB_misfolded_Ub6_Proteasome] + [ATP] → 6.0 × [Ub] + [Proteasome] + [ADP];  
 
 SUBDegradationUb7 [SUB_misfolded_Ub7_Proteasome] + [ATP] → 7.0 × [Ub] + [Proteasome] + [ADP];  
 
 SUBDegradationUb8 [SUB_misfolded_Ub8_Proteasome] + [ATP] → 8.0 × [Ub] + [Proteasome] + [ADP];  
 
 asynSynthesis1 [Source] → [asyn];  
 
 asynProt20Sbinding [asyn] + [Proteasome] → [asyn_Proteasome];  
 
 asynProt20Sdegradation [asyn_Proteasome] → [Proteasome];  
 
 asynLamp2aBinding [asyn] + [Lamp2a] → [asyn_Lamp2a];  
 
 asynCMAdegradation [asyn_Lamp2a] → [Lamp2a];  
 
 asynDamage [asyn] + [ROS] → [asyn_dam] + [ROS];  
 
 asyn_damParkinBinding [asyn_dam] + [Parkin] → [Parkin_asyn_dam];  
 
 asyn_damParkinRelease [Parkin_asyn_dam] → [asyn_dam] + [Parkin];  
 
 AsynMonoubiquitination [E2_Ub] + [Parkin_asyn_dam] → [Parkin_asyn_dam_Ub] + [E2];  
 
 AsynPolyubiquitination1 [Parkin_asyn_dam_Ub] + [E2_Ub] → [Parkin_asyn_dam_Ub2] + [E2];  
 
 AsynPolyubiquitination2 [Parkin_asyn_dam_Ub2] + [E2_Ub] → [Parkin_asyn_dam_Ub3] + [E2];  
 
 AsynPolyubiquitination3 [Parkin_asyn_dam_Ub3] + [E2_Ub] → [Parkin_asyn_dam_Ub4] + [E2];  
 
 AsynPolyubiquitination4 [Parkin_asyn_dam_Ub4] + [E2_Ub] → [Parkin_asyn_dam_Ub5] + [E2];  
 
 AsynPolyubiquitination5 [Parkin_asyn_dam_Ub5] + [E2_Ub] → [Parkin_asyn_dam_Ub6] + [E2];  
 
 AsynPolyubiquitination6 [Parkin_asyn_dam_Ub6] + [E2_Ub] → [Parkin_asyn_dam_Ub7] + [E2];  
 
 AsynPolyubiquitination7 [Parkin_asyn_dam_Ub7] + [E2_Ub] → [Parkin_asyn_dam_Ub8] + [E2];  
 
 AsynDUBbindingUb8 [Parkin_asyn_dam_Ub8] + [DUB] → [Parkin_asyn_dam_Ub8_DUB];  
 
 AsynDUBbindingUb7 [Parkin_asyn_dam_Ub7] + [DUB] → [Parkin_asyn_dam_Ub7_DUB];  
 
 AsynDUBbindingUb6 [Parkin_asyn_dam_Ub6] + [DUB] → [Parkin_asyn_dam_Ub6_DUB];  
 
 AsynDUBbindingUb5 [Parkin_asyn_dam_Ub5] + [DUB] → [Parkin_asyn_dam_Ub5_DUB];  
 
 AsynDUBbindingUb4 [Parkin_asyn_dam_Ub4] + [DUB] → [Parkin_asyn_dam_Ub4_DUB];  
 
 AsynDUBbindingUb3 [Parkin_asyn_dam_Ub3] + [DUB] → [Parkin_asyn_dam_Ub3_DUB];  
 
 AsynDUBbindingUb2 [Parkin_asyn_dam_Ub2] + [DUB] → [Parkin_asyn_dam_Ub2_DUB];  
 
 AsynDUBbindingUb1 [Parkin_asyn_dam_Ub] + [DUB] → [Parkin_asyn_dam_Ub_DUB];  
 
 AsynDeubiquitinationUb8 [Parkin_asyn_dam_Ub8_DUB] → [Parkin_asyn_dam_Ub7_DUB] + [Ub];  
 
 AsynDeubiquitinationUb7 [Parkin_asyn_dam_Ub7_DUB] → [Parkin_asyn_dam_Ub6_DUB] + [Ub];  
 
 AsynDeubiquitinationUb6 [Parkin_asyn_dam_Ub6_DUB] → [Parkin_asyn_dam_Ub5_DUB] + [Ub];  
 
 AsynDeubiquitinationUb5 [Parkin_asyn_dam_Ub5_DUB] → [Parkin_asyn_dam_Ub4_DUB] + [Ub];  
 
 AsynDeubiquitinationUb4 [Parkin_asyn_dam_Ub4_DUB] → [Parkin_asyn_dam_Ub3_DUB] + [Ub];  
 
 AsynDeubiquitinationUb3 [Parkin_asyn_dam_Ub3_DUB] → [Parkin_asyn_dam_Ub2_DUB] + [Ub];  
 
 AsynDeubiquitinationUb2 [Parkin_asyn_dam_Ub2_DUB] → [Parkin_asyn_dam_Ub_DUB] + [Ub];  
 
 AsynDeubiquitinationUb1 [Parkin_asyn_dam_Ub_DUB] → [Parkin_asyn_dam] + [DUB] + [Ub];  
 
 AsynProteasomeBindingUb4 [Parkin_asyn_dam_Ub4] + [Proteasome] → [asyn_dam_Ub4_Proteasome] + [Parkin];  
 
 AsynProteasomeBindingUb5 [Parkin_asyn_dam_Ub5] + [Proteasome] → [asyn_dam_Ub5_Proteasome] + [Parkin];  
 
 AsynProteasomeBindingUb6 [Parkin_asyn_dam_Ub6] + [Proteasome] → [asyn_dam_Ub6_Proteasome] + [Parkin];  
 
 AsynProteasomeBindingUb7 [Parkin_asyn_dam_Ub7] + [Proteasome] → [asyn_dam_Ub7_Proteasome] + [Parkin];  
 
 AsynProteasomeBindingUb8 [Parkin_asyn_dam_Ub8] + [Proteasome] → [asyn_dam_Ub8_Proteasome] + [Parkin];  
 
 DeubiquitinationBoundasyn_damUb8 [asyn_dam_Ub8_Proteasome] + [DUB] → [asyn_dam_Ub7_Proteasome] + [Ub] + [DUB];  
 
 DeubiquitinationBoundasynDamUb7 [asyn_dam_Ub7_Proteasome] + [DUB] → [asyn_dam_Ub6_Proteasome] + [Ub] + [DUB];  
 
 DeubiquitinationBoundasynDamUb6 [asyn_dam_Ub6_Proteasome] + [DUB] → [asyn_dam_Ub5_Proteasome] + [Ub] + [DUB];  
 
 DeubiquitinationBoundasynDamUb5 [asyn_dam_Ub5_Proteasome] + [DUB] → [asyn_dam_Ub4_Proteasome] + [Ub] + [DUB];  
 
 DeubiquitinationBoundasynDamUb4 [asyn_dam_Ub4_Proteasome] + [DUB] → [asyn_dam] + [Proteasome] + 4.0 × [Ub] + [DUB];  
 
 AsynProteasomeActivityUb4 [asyn_dam_Ub4_Proteasome] + [ATP] → 4.0 × [Ub] + [Proteasome] + [ADP];  
 
 AsynDegradationUb5 [asyn_dam_Ub5_Proteasome] + [ATP] → 5.0 × [Ub] + [Proteasome] + [ADP];  
 
 AsynDegradationUb6 [asyn_dam_Ub6_Proteasome] + [ATP] → 6.0 × [Ub] + [Proteasome] + [ADP];  
 
 AsynDegradationUb7 [asyn_dam_Ub7_Proteasome] + [ATP] → 7.0 × [Ub] + [Proteasome] + [ADP];  
 
 AsynDegradationUb8 [asyn_dam_Ub8_Proteasome] + [ATP] → 8.0 × [Ub] + [Proteasome] + [ADP];  
 
 Aggregationasyn1 2.0 × [asyn] → [AggA1];  
 
 Aggregationasyn2 [asyn] + [AggA1] → [AggA2];  
 
 Aggregationasyn3 [asyn] + [AggA2] → [AggA3];  
 
 Aggregationasyn4 [asyn] + [AggA3] → [AggA4];  
 
 Aggregationasyn5 [asyn] + [AggA4] → [AggA5];  
 
 DisAggregationasyn1 [AggA5] → [AggA4] + [asyn];  
 
 DisAggregationasyn2 [AggA4] → [AggA3] + [asyn];  
 
 DisAggregationasyn3 [AggA3] → [AggA2] + [asyn];  
 
 DisAggregationasyn4 [AggA2] → [AggA1] + [asyn];  
 
 DisAggregationasyn5 [AggA1] → 2.0 × [asyn];  
 
 AggA1ProteasomeInhibition [AggA1] + [Proteasome] → [AggP_Proteasome];  
 
 AggA2ProteasomeInhibition [AggA2] + [Proteasome] → [AggP_Proteasome];  
 
 AggA3ProteasomeInhibition [AggA3] + [Proteasome] → [AggP_Proteasome];  
 
 AggA4ProteasomeInhibition [AggA4] + [Proteasome] → [AggP_Proteasome];  
 
 AggA5ProteasomeInhibition [AggA5] + [Proteasome] → [AggP_Proteasome];  
 
 AsynInclusionFormation [asyn] + [AggA5] → [SeqAggP] + 7.0 × [aggasyn];  
 
 AsynInclusionGrowth [SeqAggP] + [asyn] → 2.0 × [SeqAggP] + [aggasyn];  
 
 ROSgenerationSmallAggA1 [AggA1] → [AggA1] + [ROS];  
 
 ROSgenerationSmallAggA2 [AggA2] → [AggA2] + [ROS];  
 
 ROSgenerationSmallAggA3 [AggA3] → [AggA3] + [ROS];  
 
 ROSgenerationSmallAggA4 [AggA4] → [AggA4] + [ROS];  
 
 ROSgenerationSmallAggA5 [AggA5] → [AggA5] + [ROS];  
 
 AggregationAsynDam1 2.0 × [asyn_dam] → [AggD1];  
 
 AggregationAsynDam2 [asyn_dam] + [AggD1] → [AggD2];  
 
 AggregationAsynDam3 [asyn_dam] + [AggD2] → [AggD3];  
 
 AggregationAsynDam4 [asyn_dam] + [AggD3] → [AggD4];  
 
 AggregationAsynDam5 [asyn_dam] + [AggD4] → [AggD5];  
 
 DisaggregationAsynDam1 [AggD5] → [AggD4] + [asyn_dam];  
 
 DisaggregationAsynDam2 [AggD4] → [AggD3] + [asyn_dam];  
 
 DisaggregationAsynDam3 [AggD3] → [AggD2] + [asyn_dam];  
 
 DisaggregationAsynDam4 [AggD2] → [AggD1] + [asyn_dam];  
 
 DisaggregationAsynDam5 [AggD1] → 2.0 × [asyn_dam];  
 
 AggD1ProteasomeInhibition [AggD1] + [Proteasome] → [AggP_Proteasome];  
 
 AggD2ProteasomeInhibition [AggD2] + [Proteasome] → [AggP_Proteasome];  
 
 AggD3ProteasomeInhibition [AggD3] + [Proteasome] → [AggP_Proteasome];  
 
 AggD4ProteasomeInhibition [AggD4] + [Proteasome] → [AggP_Proteasome];  
 
 AggD5ProteasomeInhibition [AggD5] + [Proteasome] → [AggP_Proteasome];  
 
 AsynDamInclusionFormation [asyn_dam] + [AggD5] → [SeqAggP] + 7.0 × [aggasyndam];  
 
 AsynDamInclusionGrowth1 [SeqAggP] + [asyn_dam] → 2.0 × [SeqAggP] + [aggasyndam];  
 
 AsynDamInclusionGrowth2 [SeqAggP] + [Parkin_asyn_dam] → 2.0 × [SeqAggP] + [aggasyndam] + [aggParkin];  
 
 AsynDamInclusionGrowth3 [SeqAggP] + [Parkin_asyn_dam_Ub] → 2.0 × [SeqAggP] + [aggasyndam] + [aggUb] + [aggParkin];  
 
 AsynDamInclusionGrowth4 [SeqAggP] + [Parkin_asyn_dam_Ub2] → 2.0 × [SeqAggP] + [aggasyndam] + 2.0 × [aggUb] + [aggParkin];  
 
 AsynDamInclusionGrowth5 [SeqAggP] + [Parkin_asyn_dam_Ub3] → 2.0 × [SeqAggP] + [aggasyndam] + 3.0 × [aggUb] + [aggParkin];  
 
 AsynDamInclusionGrowth6 [SeqAggP] + [Parkin_asyn_dam_Ub4] → 2.0 × [SeqAggP] + [aggasyndam] + 4.0 × [aggUb] + [aggParkin];  
 
 AsynDamInclusionGrowth7 [SeqAggP] + [Parkin_asyn_dam_Ub5] → 2.0 × [SeqAggP] + [aggasyndam] + 5.0 × [aggUb] + [aggParkin];  
 
 AsynDamInclusionGrowth8 [SeqAggP] + [Parkin_asyn_dam_Ub6] → 2.0 × [SeqAggP] + [aggasyndam] + 6.0 × [aggUb] + [aggParkin];  
 
 AsynDamInclusionGrowth9 [SeqAggP] + [Parkin_asyn_dam_Ub7] → 2.0 × [SeqAggP] + [aggasyndam] + 7.0 × [aggUb] + [aggParkin];  
 
 AsynDamInclusionGrowth10 [SeqAggP] + [Parkin_asyn_dam_Ub8] → 2.0 × [SeqAggP] + [aggasyndam] + 8.0 × [aggUb] + [aggParkin];  
 
 AsynDamInclusionGrowth11 [SeqAggP] + [Parkin_asyn_dam_Ub_DUB] → 2.0 × [SeqAggP] + [aggasyndam] + [aggUb] + [aggParkin];  
 
 AsynDamInclusionGrowth12 [SeqAggP] + [Parkin_asyn_dam_Ub2_DUB] → 2.0 × [SeqAggP] + [aggasyndam] + 2.0 × [aggUb] + [aggParkin];  
 
 AsynDamInclusionGrowth13 [SeqAggP] + [Parkin_asyn_dam_Ub3_DUB] → 2.0 × [SeqAggP] + [aggasyndam] + 3.0 × [aggUb] + [aggParkin];  
 
 AsynDamInclusionGrowth14 [SeqAggP] + [Parkin_asyn_dam_Ub4_DUB] → 2.0 × [SeqAggP] + [aggasyndam] + 4.0 × [aggUb] + [aggParkin];  
 
 AsynDamInclusionGrowth15 [SeqAggP] + [Parkin_asyn_dam_Ub5_DUB] → 2.0 × [SeqAggP] + [aggasyndam] + 5.0 × [aggUb] + [aggParkin];  
 
 AsynDamInclusionGrowth16 [SeqAggP] + [Parkin_asyn_dam_Ub6_DUB] → 2.0 × [SeqAggP] + [aggasyndam] + 6.0 × [aggUb] + [aggParkin];  
 
 AsynDamInclusionGrowth17 [SeqAggP] + [Parkin_asyn_dam_Ub7_DUB] → 2.0 × [SeqAggP] + [aggasyndam] + 7.0 × [aggUb] + [aggParkin];  
 
 AsynDamInclusionGrowth18 [SeqAggP] + [Parkin_asyn_dam_Ub8_DUB] → 2.0 × [SeqAggP] + [aggasyndam] + 8.0 × [aggUb] + [aggParkin];  
 
 ROSgenerationSmallAggD1 [AggD1] → [AggD1] + [ROS];  
 
 ROSgenerationSmallAggD2 [AggD2] → [AggD2] + [ROS];  
 
 ROSgenerationSmallAggD3 [AggD3] → [AggD3] + [ROS];  
 
 ROSgenerationSmallAggD4 [AggD4] → [AggD4] + [ROS];  
 
 ROSgenerationSmallAggD5 [AggD5] → [AggD5] + [ROS];  
 
 AggregationUCHL1Dam1 2.0 × [UCHL1_damaged] → [AggU1];  
 
 AggregationUCHL1Dam2 [UCHL1_damaged] + [AggU1] → [AggU2];  
 
 AggregationUCHL1Dam3 [UCHL1_damaged] + [AggU2] → [AggU3];  
 
 AggregationUCHL1Dam4 [UCHL1_damaged] + [AggU3] → [AggU4];  
 
 AggregationUCHL1Dam5 [UCHL1_damaged] + [AggU4] → [AggU5];  
 
 DisaggregationUCHL1Dam1 [AggU5] → [AggU4] + [UCHL1_damaged];  
 
 DisaggregationUCHL1Dam2 [AggU4] → [AggU3] + [UCHL1_damaged];  
 
 DisaggregationUCHL1Dam3 [AggU3] → [AggU2] + [UCHL1_damaged];  
 
 DisaggregationUCHL1Dam4 [AggU2] → [AggU1] + [UCHL1_damaged];  
 
 DisaggregationUCHL1Dam5 [AggU1] → 2.0 × [UCHL1_damaged];  
 
 AggU1ProteasomeInhibition [AggU1] + [Proteasome] → [AggP_Proteasome];  
 
 AggU2ProteasomeInhibition [AggU2] + [Proteasome] → [AggP_Proteasome];  
 
 AggU3ProteasomeInhibition [AggU3] + [Proteasome] → [AggP_Proteasome];  
 
 AggU4ProteasomeInhibition [AggU4] + [Proteasome] → [AggP_Proteasome];  
 
 AggU5ProteasomeInhibition [AggU5] + [Proteasome] → [AggP_Proteasome];  
 
 UCHL1DamInclusionFormation [UCHL1_damaged] + [AggU5] → [SeqAggP] + 7.0 × [aggUchl1dam];  
 
 UCHL1DamagedSequestering [SeqAggP] + [UCHL1_damaged] → 2.0 × [SeqAggP] + [aggUchl1dam];  
 
 UCHL1DamagedLamp2aSequestering [SeqAggP] + [Lamp2a_UCHL1_damaged] → 2.0 × [SeqAggP] + [aggUchl1dam];  
 
 ROSgenerationSmallAggU1 [AggU1] → [AggU1] + [ROS];  
 
 ROSgenerationSmallAggU2 [AggU2] → [AggU2] + [ROS];  
 
 ROSgenerationSmallAggU3 [AggU3] → [AggU3] + [ROS];  
 
 ROSgenerationSmallAggU4 [AggU4] → [AggU4] + [ROS];  
 
 ROSgenerationSmallAggU5 [AggU5] → [AggU5] + [ROS];  
 
 SUBAggregation1 2.0 × [SUB_misfolded] → [AggS1];  
 
 SUBAggregation2 [SUB_misfolded] + [AggS1] → [AggS2];  
 
 SUBAggregation3 [SUB_misfolded] + [AggS2] → [AggS3];  
 
 SUBAggregation4 [SUB_misfolded] + [AggS3] → [AggS4];  
 
 SUBAggregation5 [SUB_misfolded] + [AggS4] → [AggS5];  
 
 SUBDisaggregation1 [AggS5] → [AggS4] + [SUB_misfolded];  
 
 SUBDisaggregation2 [AggS4] → [AggS3] + [SUB_misfolded];  
 
 SUBDisaggregation3 [AggS3] → [AggS2] + [SUB_misfolded];  
 
 SUBDisaggregation4 [AggS2] → [AggS1] + [SUB_misfolded];  
 
 SUBDisaggregation5 [AggS1] → 2.0 × [SUB_misfolded];  
 
 AggS1ProteasomeInhibition [AggS1] + [Proteasome] → [AggP_Proteasome];  
 
 AggS2ProteasomeInhibition [AggS2] + [Proteasome] → [AggP_Proteasome];  
 
 AggS3ProteasomeInhibition [AggS3] + [Proteasome] → [AggP_Proteasome];  
 
 AggS4ProteasomeInhibition [AggS4] + [Proteasome] → [AggP_Proteasome];  
 
 AggS5ProteasomeInhibition [AggS5] + [Proteasome] → [AggP_Proteasome];  
 
 SUBInclusionFormation [AggS5] + [SUB_misfolded] → [SeqAggP] + 7.0 × [aggSUB];  
 
 SUBInclusionGrowth0 [SeqAggP] + [SUB_misfolded] → 2.0 × [SeqAggP] + [aggSUB];  
 
 SUBInclusionGrowth1 [E3SUB_SUB_misfolded] + [SeqAggP] → 2.0 × [SeqAggP] + [aggSUB];  
 
 SUBInclusionGrowth2 [E3SUB_SUB_misfolded_Ub] + [SeqAggP] → 2.0 × [SeqAggP] + [aggSUB] + [aggUb];  
 
 SUBInclusionGrowth3 [E3SUB_SUB_misfolded_Ub2] + [SeqAggP] → 2.0 × [SeqAggP] + [aggSUB] + 2.0 × [aggUb];  
 
 SUBInclusionGrowth4 [E3SUB_SUB_misfolded_Ub3] + [SeqAggP] → 2.0 × [SeqAggP] + [aggSUB] + 3.0 × [aggUb];  
 
 SUBInclusionGrowth5 [E3SUB_SUB_misfolded_Ub4] + [SeqAggP] → 2.0 × [SeqAggP] + [aggSUB] + 4.0 × [aggUb];  
 
 SUBInclusionGrowth6 [E3SUB_SUB_misfolded_Ub5] + [SeqAggP] → 2.0 × [SeqAggP] + [aggSUB] + 5.0 × [aggUb];  
 
 SUBInclusionGrowth7 [E3SUB_SUB_misfolded_Ub6] + [SeqAggP] → 2.0 × [SeqAggP] + [aggSUB] + 6.0 × [aggUb];  
 
 SUBInclusionGrowth8 [E3SUB_SUB_misfolded_Ub7] + [SeqAggP] → 2.0 × [SeqAggP] + [aggSUB] + 7.0 × [aggUb];  
 
 SUBInclusionGrowth9 [E3SUB_SUB_misfolded_Ub8] + [SeqAggP] → 2.0 × [SeqAggP] + [aggSUB] + 8.0 × [aggUb];  
 
 SUBInclusionGrowth10 [E3SUB_SUB_misfolded_Ub_UCHL1] + [SeqAggP] → 2.0 × [SeqAggP] + [aggSUB] + [aggUchl1] + [aggUb];  
 
 SUBInclusionGrowth11 [E3SUB_SUB_misfolded_Ub2_UCHL1] + [SeqAggP] → 2.0 × [SeqAggP] + [aggSUB] + [aggUchl1] + 2.0 × [aggUb];  
 
 SUBInclusionGrowth12 [E3SUB_SUB_misfolded_Ub3_UCHL1] + [SeqAggP] → 2.0 × [SeqAggP] + [aggSUB] + [aggUchl1] + 3.0 × [aggUb];  
 
 SUBInclusionGrowth13 [E3SUB_SUB_misfolded_Ub4_UCHL1] + [SeqAggP] → 2.0 × [SeqAggP] + [aggSUB] + [aggUchl1] + 4.0 × [aggUb];  
 
 SUBInclusionGrowth14 [E3SUB_SUB_misfolded_Ub5_UCHL1] + [SeqAggP] → 2.0 × [SeqAggP] + [aggSUB] + [aggUchl1] + 5.0 × [aggUb];  
 
 SUBInclusionGrowth15 [E3SUB_SUB_misfolded_Ub6_UCHL1] + [SeqAggP] → 2.0 × [SeqAggP] + [aggSUB] + [aggUchl1] + 6.0 × [aggUb];  
 
 SUBInclusionGrowth16 [E3SUB_SUB_misfolded_Ub7_UCHL1] + [SeqAggP] → 2.0 × [SeqAggP] + [aggSUB] + [aggUchl1] + 7.0 × [aggUb];  
 
 SUBInclusionGrowth17 [E3SUB_SUB_misfolded_Ub8_UCHL1] + [SeqAggP] → 2.0 × [SeqAggP] + [aggSUB] + [aggUchl1] + 8.0 × [aggUb];  
 
 ROSgenerationSmallAggS1 [AggS1] → [AggS1] + [ROS];  
 
 ROSgenerationSmallAggS2 [AggS2] → [AggS2] + [ROS];  
 
 ROSgenerationSmallAggS3 [AggS3] → [AggS3] + [ROS];  
 
 ROSgenerationSmallAggS4 [AggS4] → [AggS4] + [ROS];  
 
 ROSgenerationSmallAggS5 [AggS5] → [AggS5] + [ROS];  
 
 radicalFormation [Source] → [ROS];  
 
 radicalScavenging [ROS] → [Sink];  
 
Rules (9)
 
 Assignment Rule (name: Tot_MisP) Tot_MisP = E3_MisP+E3_MisP_Ub+E3_MisP_Ub_DUB+E3_MisP_Ub2+E3_MisP_Ub2_DUB+E3_MisP_Ub3+E3_MisP_Ub3_DUB+E3_MisP_Ub4+E3_MisP_Ub4_DUB+E3_MisP_Ub5+E3_MisP_Ub5_DUB+E3_MisP_Ub6+E3_MisP_Ub6_DUB+E3_MisP_Ub7+E3_MisP_Ub7_DUB+E3_MisP_Ub8+E3_MisP_Ub8_DUB+MisP+MisP_Ub4_Proteasome+MisP_Ub5_Proteasome+MisP_Ub6_Proteasome+MisP_Ub7_Proteasome+MisP_Ub8_Proteasome
 
 Assignment Rule (name: Tot_Protein) Tot_Protein = Tot_MisP+NatP
 
 Assignment Rule (name: Ub_Conjugates) Ub_Conjugates = aggUb+4*asyn_dam_Ub4_Proteasome+5*asyn_dam_Ub5_Proteasome+6*asyn_dam_Ub6_Proteasome+7*asyn_dam_Ub7_Proteasome+8*asyn_dam_Ub8_Proteasome+E1_Ub+E2_Ub+E3_MisP_Ub+E3_MisP_Ub_DUB+2*E3_MisP_Ub2+2*E3_MisP_Ub2_DUB+3*E3_MisP_Ub3+3*E3_MisP_Ub3_DUB+4*E3_MisP_Ub4+4*E3_MisP_Ub4_DUB+5*E3_MisP_Ub5+5*E3_MisP_Ub5_DUB+6*E3_MisP_Ub6+6*E3_MisP_Ub6_DUB+7*E3_MisP_Ub7+7*E3_MisP_Ub7_DUB+8*E3_MisP_Ub8+8*E3_MisP_Ub8_DUB+E3SUB_SUB_misfolded_Ub+E3SUB_SUB_misfolded_Ub_UCHL1+2*E3SUB_SUB_misfolded_Ub2+2*E3SUB_SUB_misfolded_Ub2_UCHL1+3*E3SUB_SUB_misfolded_Ub3+3*E3SUB_SUB_misfolded_Ub3_UCHL1+4*E3SUB_SUB_misfolded_Ub4+4*E3SUB_SUB_misfolded_Ub4_UCHL1+5*E3SUB_SUB_misfolded_Ub5+5*E3SUB_SUB_misfolded_Ub5_UCHL1+6*E3SUB_SUB_misfolded_Ub6+6*E3SUB_SUB_misfolded_Ub6_UCHL1+7*E3SUB_SUB_misfolded_Ub7+7*E3SUB_SUB_misfolded_Ub7_UCHL1+8*E3SUB_SUB_misfolded_Ub8+8*E3SUB_SUB_misfolded_Ub8_UCHL1+E3SUB_SUB_misfolded_Ub_UCHL1+4*MisP_Ub4_Proteasome+5*MisP_Ub5_Proteasome+6*MisP_Ub6_Proteasome+7*MisP_Ub7_Proteasome+8*MisP_Ub8_Proteasome+Parkin_asyn_dam_Ub+Parkin_asyn_dam_Ub_DUB+2*Parkin_asyn_dam_Ub2+2*Parkin_asyn_dam_Ub2_DUB+3*Parkin_asyn_dam_Ub3+3*Parkin_asyn_dam_Ub3_DUB+4*Parkin_asyn_dam_Ub4+4*Parkin_asyn_dam_Ub4_DUB+5*Parkin_asyn_dam_Ub5+5*Parkin_asyn_dam_Ub5_DUB+6*Parkin_asyn_dam_Ub6+6*Parkin_asyn_dam_Ub6_DUB+7*Parkin_asyn_dam_Ub7+7*Parkin_asyn_dam_Ub7_DUB+8*Parkin_asyn_dam_Ub8+8*Parkin_asyn_dam_Ub8_DUB+4*SUB_misfolded_Ub4_Proteasome+5*SUB_misfolded_Ub5_Proteasome+6*SUB_misfolded_Ub6_Proteasome+7*SUB_misfolded_Ub7_Proteasome+8*SUB_misfolded_Ub8_Proteasome+Ub_UCHL1+upregUb
 
 Assignment Rule (name: Tot_Ub) Tot_Ub = Ub_Conjugates+Ub
 
 Assignment Rule (name: AggP) AggP = AggA1+AggA2+AggA3+AggA4+AggA5+aggasyn+aggasyndam+AggD1+AggD2+AggD3+AggD4+AggD5+aggDUB+aggE3+aggMisP+AggP1+AggP2+AggP3+AggP4+AggP5+aggParkin+AggS1+AggS2+AggS3+AggS4+AggS5+aggSUB+AggU1+AggU2+AggU3+AggU4+AggU5+aggUb+aggUchl1+aggUchl1dam
 
 Assignment Rule (name: Tot_asyn_dam) Tot_asyn_dam = asyn_dam+asyn_dam_Ub4_Proteasome+asyn_dam_Ub5_Proteasome+asyn_dam_Ub6_Proteasome+asyn_dam_Ub7_Proteasome+asyn_dam_Ub8_Proteasome+asyn_dam_Ub4_Proteasome+Parkin_asyn_dam+Parkin_asyn_dam_Ub+Parkin_asyn_dam_Ub_DUB+Parkin_asyn_dam_Ub2+Parkin_asyn_dam_Ub2_DUB+Parkin_asyn_dam_Ub3+Parkin_asyn_dam_Ub3_DUB+Parkin_asyn_dam_Ub4+Parkin_asyn_dam_Ub4_DUB+Parkin_asyn_dam_Ub5+Parkin_asyn_dam_Ub5_DUB+Parkin_asyn_dam_Ub6+Parkin_asyn_dam_Ub6_DUB+Parkin_asyn_dam_Ub7+Parkin_asyn_dam_Ub7_DUB+Parkin_asyn_dam_Ub8+Parkin_asyn_dam_Ub8_DUB
 
 Assignment Rule (name: Tot_asyn) Tot_asyn = asyn+asyn_Lamp2a+asyn_Proteasome
 
 Assignment Rule (name: UCHL1_substrate) UCHL1_substrate = E3SUB_SUB_misfolded_Ub_UCHL1+E3SUB_SUB_misfolded_Ub2_UCHL1+E3SUB_SUB_misfolded_Ub3_UCHL1+E3SUB_SUB_misfolded_Ub4_UCHL1+E3SUB_SUB_misfolded_Ub5_UCHL1+E3SUB_SUB_misfolded_Ub6_UCHL1+E3SUB_SUB_misfolded_Ub7_UCHL1+E3SUB_SUB_misfolded_Ub8_UCHL1+Lamp2a_UCHL1_damaged+Ub_UCHL1+UCHL1_damaged+UCHL1_damaged_Proteasome+UCHL1_Proteasome
 
 Assignment Rule (name: Tot_UCHL1) Tot_UCHL1 = UCHL1+UCHL1_substrate
 
   Spatial dimensions: 3.0  Compartment size: 1.0
 
 NatP
Compartment: cytosol
Initial amount: 6000.0
 
 MisP
Compartment: cytosol
Initial amount: 80.0
 
 Ub
Compartment: cytosol
Initial amount: 1500.0
 
 E1
Compartment: cytosol
Initial amount: 105.0
 
 E2
Compartment: cytosol
Initial amount: 50.0
 
 E3
Compartment: cytosol
Initial amount: 300.0
 
 E3_MisP
Compartment: cytosol
Initial amount: 2.0
 
 DUB
Compartment: cytosol
Initial amount: 160.0
 
 Proteasome
Compartment: cytosol
Initial amount: 1500.0
 
 ROS
Compartment: cytosol
Initial amount: 10.0
 
 E1_Ub
Compartment: cytosol
Initial amount: 795.0
 
 E2_Ub
Compartment: cytosol
Initial amount: 950.0
 
 E3_MisP_Ub
Compartment: cytosol
Initial amount: 0.0
 
 E3_MisP_Ub2
Compartment: cytosol
Initial amount: 0.0
 
 E3_MisP_Ub3
Compartment: cytosol
Initial amount: 0.0
 
 E3_MisP_Ub4
Compartment: cytosol
Initial amount: 0.0
 
 E3_MisP_Ub5
Compartment: cytosol
Initial amount: 0.0
 
 E3_MisP_Ub6
Compartment: cytosol
Initial amount: 0.0
 
 E3_MisP_Ub7
Compartment: cytosol
Initial amount: 0.0
 
 E3_MisP_Ub8
Compartment: cytosol
Initial amount: 300.0
 
 MisP_Ub4_Proteasome
Compartment: cytosol
Initial amount: 0.0
 
 MisP_Ub5_Proteasome
Compartment: cytosol
Initial amount: 1.0
 
 MisP_Ub6_Proteasome
Compartment: cytosol
Initial amount: 2.0
 
 MisP_Ub7_Proteasome
Compartment: cytosol
Initial amount: 10.0
 
 MisP_Ub8_Proteasome
Compartment: cytosol
Initial amount: 350.0
 
 E3_MisP_Ub_DUB
Compartment: cytosol
Initial amount: 100.0
 
 E3_MisP_Ub2_DUB
Compartment: cytosol
Initial amount: 100.0
 
 E3_MisP_Ub3_DUB
Compartment: cytosol
Initial amount: 100.0
 
 E3_MisP_Ub4_DUB
Compartment: cytosol
Initial amount: 100.0
 
 E3_MisP_Ub5_DUB
Compartment: cytosol
Initial amount: 100.0
 
 E3_MisP_Ub6_DUB
Compartment: cytosol
Initial amount: 100.0
 
 E3_MisP_Ub7_DUB
Compartment: cytosol
Initial amount: 100.0
 
 E3_MisP_Ub8_DUB
Compartment: cytosol
Initial amount: 100.0
 
 AggP1
Compartment: cytosol
Initial amount: 0.0
 
 AggP2
Compartment: cytosol
Initial amount: 0.0
 
 AggP3
Compartment: cytosol
Initial amount: 0.0
 
 AggP4
Compartment: cytosol
Initial amount: 0.0
 
 AggP5
Compartment: cytosol
Initial amount: 0.0
 
 SeqAggP
Compartment: cytosol
Initial amount: 0.0
 
 AggP_Proteasome
Compartment: cytosol
Initial amount: 0.0
 
 ATP
Compartment: cytosol
Initial amount: 10000.0
Constant
 
 ADP
Compartment: cytosol
Initial amount: 1000.0
Constant
 
 AMP
Compartment: cytosol
Initial amount: 1000.0
Constant
 
 UCHL1
Compartment: cytosol
Initial amount: 5785.0
 
 UCHL1_Proteasome
Compartment: cytosol
Initial amount: 10.0
 
 UCHL1_damaged_Proteasome
Compartment: cytosol
Initial amount: 0.0
 
 Lysosome
Compartment: cytosol
Initial amount: 1200.0
 
 UCHL1_damaged
Compartment: cytosol
Initial amount: 0.0
 
 Lamp2a
Compartment: cytosol
Initial amount: 200.0
 
 Lamp2a_UCHL1_damaged
Compartment: cytosol
Initial amount: 0.0
 
 Ub_UCHL1
Compartment: cytosol
Initial amount: 500.0
 
 SUB
Compartment: cytosol
Initial amount: 815.0
 
 SUB_misfolded
Compartment: cytosol
Initial amount: 5.0
 
 E3SUB
Compartment: cytosol
Initial amount: 160.0
 
 E3SUB_SUB_misfolded
Compartment: cytosol
Initial amount: 5.0
 
 E3SUB_SUB_misfolded_Ub
Compartment: cytosol
Initial amount: 0.0
 
 E3SUB_SUB_misfolded_Ub2
Compartment: cytosol
Initial amount: 0.0
 
 E3SUB_SUB_misfolded_Ub3
Compartment: cytosol
Initial amount: 0.0
 
 E3SUB_SUB_misfolded_Ub4
Compartment: cytosol
Initial amount: 0.0
 
 E3SUB_SUB_misfolded_Ub5
Compartment: cytosol
Initial amount: 0.0
 
 E3SUB_SUB_misfolded_Ub6
Compartment: cytosol
Initial amount: 0.0
 
 E3SUB_SUB_misfolded_Ub7
Compartment: cytosol
Initial amount: 0.0
 
 E3SUB_SUB_misfolded_Ub8
Compartment: cytosol
Initial amount: 15.0
 
 E3SUB_SUB_misfolded_Ub_UCHL1
Compartment: cytosol
Initial amount: 20.0
 
 E3SUB_SUB_misfolded_Ub2_UCHL1
Compartment: cytosol
Initial amount: 20.0
 
 E3SUB_SUB_misfolded_Ub3_UCHL1
Compartment: cytosol
Initial amount: 25.0
 
 E3SUB_SUB_misfolded_Ub4_UCHL1
Compartment: cytosol
Initial amount: 25.0
 
 E3SUB_SUB_misfolded_Ub5_UCHL1
Compartment: cytosol
Initial amount: 30.0
 
 E3SUB_SUB_misfolded_Ub6_UCHL1
Compartment: cytosol
Initial amount: 30.0
 
 E3SUB_SUB_misfolded_Ub7_UCHL1
Compartment: cytosol
Initial amount: 40.0
 
 E3SUB_SUB_misfolded_Ub8_UCHL1
Compartment: cytosol
Initial amount: 40.0
 
 SUB_misfolded_Ub4_Proteasome
Compartment: cytosol
Initial amount: 0.0
 
 SUB_misfolded_Ub5_Proteasome
Compartment: cytosol
Initial amount: 0.0
 
 SUB_misfolded_Ub6_Proteasome
Compartment: cytosol
Initial amount: 0.0
 
 SUB_misfolded_Ub7_Proteasome
Compartment: cytosol
Initial amount: 5.0
 
 SUB_misfolded_Ub8_Proteasome
Compartment: cytosol
Initial amount: 20.0
 
 asyn
Compartment: cytosol
Initial amount: 3000.0
 
 asyn_Proteasome
Compartment: cytosol
Initial amount: 0.0
 
 asyn_Lamp2a
Compartment: cytosol
Initial amount: 0.0
 
 asyn_dam
Compartment: cytosol
Initial amount: 0.0
 
 Parkin
Compartment: cytosol
Initial amount: 4800.0
 
 Parkin_asyn_dam
Compartment: cytosol
Initial amount: 0.0
 
 Parkin_asyn_dam_Ub
Compartment: cytosol
Initial amount: 0.0
 
 Parkin_asyn_dam_Ub2
Compartment: cytosol
Initial amount: 0.0
 
 Parkin_asyn_dam_Ub3
Compartment: cytosol
Initial amount: 0.0
 
 Parkin_asyn_dam_Ub4
Compartment: cytosol
Initial amount: 0.0
 
 Parkin_asyn_dam_Ub5
Compartment: cytosol
Initial amount: 0.0
 
 Parkin_asyn_dam_Ub6
Compartment: cytosol
Initial amount: 0.0
 
 Parkin_asyn_dam_Ub7
Compartment: cytosol
Initial amount: 0.0
 
 Parkin_asyn_dam_Ub8
Compartment: cytosol
Initial amount: 0.0
 
 Parkin_asyn_dam_Ub_DUB
Compartment: cytosol
Initial amount: 0.0
 
 Parkin_asyn_dam_Ub2_DUB
Compartment: cytosol
Initial amount: 0.0
 
 Parkin_asyn_dam_Ub3_DUB
Compartment: cytosol
Initial amount: 0.0
 
 Parkin_asyn_dam_Ub4_DUB
Compartment: cytosol
Initial amount: 0.0
 
 Parkin_asyn_dam_Ub5_DUB
Compartment: cytosol
Initial amount: 0.0
 
 Parkin_asyn_dam_Ub6_DUB
Compartment: cytosol
Initial amount: 0.0
 
 Parkin_asyn_dam_Ub7_DUB
Compartment: cytosol
Initial amount: 0.0
 
 Parkin_asyn_dam_Ub8_DUB
Compartment: cytosol
Initial amount: 0.0
 
 asyn_dam_Ub4_Proteasome
Compartment: cytosol
Initial amount: 0.0
 
 asyn_dam_Ub5_Proteasome
Compartment: cytosol
Initial amount: 0.0
 
 asyn_dam_Ub6_Proteasome
Compartment: cytosol
Initial amount: 0.0
 
 asyn_dam_Ub7_Proteasome
Compartment: cytosol
Initial amount: 0.0
 
 asyn_dam_Ub8_Proteasome
Compartment: cytosol
Initial amount: 0.0
 
 AggA1
Compartment: cytosol
Initial amount: 0.0
 
 AggA2
Compartment: cytosol
Initial amount: 0.0
 
 AggA3
Compartment: cytosol
Initial amount: 0.0
 
 AggA4
Compartment: cytosol
Initial amount: 0.0
 
 AggA5
Compartment: cytosol
Initial amount: 0.0
 
 AggD1
Compartment: cytosol
Initial amount: 0.0
 
 AggD2
Compartment: cytosol
Initial amount: 0.0
 
 AggD3
Compartment: cytosol
Initial amount: 0.0
 
 AggD4
Compartment: cytosol
Initial amount: 0.0
 
 AggD5
Compartment: cytosol
Initial amount: 0.0
 
 AggU1
Compartment: cytosol
Initial amount: 0.0
 
 AggU2
Compartment: cytosol
Initial amount: 0.0
 
 AggU3
Compartment: cytosol
Initial amount: 0.0
 
 AggU4
Compartment: cytosol
Initial amount: 0.0
 
 AggU5
Compartment: cytosol
Initial amount: 0.0
 
 AggS1
Compartment: cytosol
Initial amount: 0.0
 
 AggS2
Compartment: cytosol
Initial amount: 0.0
 
 AggS3
Compartment: cytosol
Initial amount: 0.0
 
 AggS4
Compartment: cytosol
Initial amount: 0.0
 
 AggS5
Compartment: cytosol
Initial amount: 0.0
 
 Source
Compartment: cytosol
Initial amount: 1.0
Constant
 
 Sink
Compartment: cytosol
Initial amount: 1.0
Constant
 
 aggasyn
Compartment: cytosol
Initial amount: 0.0
 
 aggasyndam
Compartment: cytosol
Initial amount: 0.0
 
 aggParkin
Compartment: cytosol
Initial amount: 0.0
 
 aggUb
Compartment: cytosol
Initial amount: 0.0
 
 aggE3
Compartment: cytosol
Initial amount: 0.0
 
 aggDUB
Compartment: cytosol
Initial amount: 0.0
 
 aggMisP
Compartment: cytosol
Initial amount: 0.0
 
 aggUchl1
Compartment: cytosol
Initial amount: 0.0
 
 aggUchl1dam
Compartment: cytosol
Initial amount: 0.0
 
 aggSUB
Compartment: cytosol
Initial amount: 0.0
 
 upregUb
Compartment: cytosol
Initial amount: 0.0
 
Global Parameters (92)
 
 ksynNatP
Value: 2.4
Constant
 
 kmisfold
Value: 4.0E-5
Constant
 
 krefold
Value: 8.0E-5
Constant
 
 kbinMisPE3
Value: 1.0E-4
Constant
 
 krelMisPE3
Value: 2.0E-4
Constant
 
 kbinE1Ub
Value: 2.0E-4
Constant
 
 kbinE2Ub
Value: 0.001
Constant
 
 kmonoUb
Value: 0.001
Constant
 
 kpolyUb
Value: 0.01
Constant
 
 kactDUB
Value: 1.0E-4
Constant
 
 kbinProt
Value: 5.0E-6
Constant
 
 kactDUBProt
Value: 1.0E-6
Constant
 
 kactProt
Value: 0.01
Constant
 
 kagg1
Value: 1.0E-12
Constant
 
 kagg2
Value: 1.0E-10
Constant
 
 kdisagg1
Value: 1.0E-8
Constant
 
 kdisagg2
Value: 8.0E-9
Constant
 
 kdisagg3
Value: 6.0E-9
Constant
 
 kdisagg4
Value: 4.0E-9
Constant
 
 kdisagg5
Value: 2.0E-9
Constant
 
 kigrowth1
Value: 5.0E-9
Constant
 
 kigrowth2
Value: 5.0E-9
Constant
 
 kbinAggProt
Value: 5.0E-9
Constant
 
 kbinMisPDUB
Value: 2.0E-7
Constant
 
 kgenROS
Value: 0.01
Constant
 
 kremROS
Value: 0.001
Constant
 
 kubs
Value: 0.009
Constant
 
 kubd
Value: 4.4E-9
Constant
 
 kubss
Value: 0.1
Constant
 
 ksynUCHL1
Value: 0.022
Constant
 
 kbinUCHL1Prot
Value: 4.0E-10
Constant
 
 kdegProtUCHL1
Value: 0.01
Constant
 
 kdegLysUCHL1
Value: 2.7E-9
Constant
 
 kdamUCHL1
Value: 1.0E-8
Constant
 
 kbinLamp2aUCHL1dam
Value: 1.0E-5
Constant
 
 krelLamp2aUCHL1dam
Value: 5.0E-5
Constant
 
 kdegLysUCHL1dam
Value: 2.7E-9
Constant
 
 kbinUbUCHL1
Value: 3.0E-6
Constant
 
 krelUbUCHL1
Value: 0.05
Constant
 
 kactUchl1
Value: 1.0E-4
Constant
 
 kbinSUBUCHL1
Value: 4.0E-8
Constant
 
 ksynSUB
Value: 0.13
Constant
 
 kmisfoldSUB
Value: 2.0E-5
Constant
 
 krefoldSUB
Value: 5.0E-5
Constant
 
 kbinE3SUB
Value: 5.0E-4
Constant
 
 krelE3SUB
Value: 2.0E-4
Constant
 
 ksynasyn
Value: 0.028
Constant
 
 kbinasynProt
Value: 1.7E-9
Constant
 
 kdegasynProt
Value: 0.01
Constant
 
 kbinasynLamp2a
Value: 4.0E-8
Constant
 
 kCMAasyn
Value: 0.001
Constant
 
 kdamasyn
Value: 5.0E-8
Constant
 
 kbinasynDUB
Value: 2.0E-7
Constant
 
 kbinasynParkin
Value: 1.0E-4
Constant
 
 krelasynParkin
Value: 2.0E-4
Constant
 
 kaggasyn1
Value: 5.0E-12
Constant
 
 kaggasyn2
Value: 5.0E-10
Constant
 
 kdisaggasyn1
Value: 1.0E-8
Constant
 
 kdisaggasyn2
Value: 8.0E-9
Constant
 
 kdisaggasyn3
Value: 6.0E-9
Constant
 
 kdisaggasyn4
Value: 4.0E-9
Constant
 
 kdisaggasyn5
Value: 2.0E-9
Constant
 
 kgenROSAggP
Value: 2.0E-5
Constant
 
 kagg1dam
Value: 1.0E-5
Constant
 
 kagg2dam
Value: 0.005
Constant
 
 kdisaggasyndam1
Value: 1.0E-8
Constant
 
 kdisaggasyndam2
Value: 8.0E-9
Constant
 
 kdisaggasyndam3
Value: 6.0E-9
Constant
 
 kdisaggasyndam4
Value: 4.0E-9
Constant
 
 kdisaggasyndam5
Value: 2.0E-9
Constant
 
 kdisagguchl1dam1
Value: 1.0E-8
Constant
 
 kdisagguchl1dam2
Value: 8.0E-9
Constant
 
 kdisagguchl1dam3
Value: 6.0E-9
Constant
 
 kdisagguchl1dam4
Value: 4.0E-9
Constant
 
 kdisagguchl1dam5
Value: 2.0E-9
Constant
 
 kaggSUB1
Value: 1.0E-12
Constant
 
 kaggSUB2
Value: 1.0E-10
Constant
 
 kdisaggSUB1
Value: 1.0E-8
Constant
 
 kdisaggSUB2
Value: 8.0E-9
Constant
 
 kdisaggSUB3
Value: 6.0E-9
Constant
 
 kdisaggSUB4
Value: 4.0E-9
Constant
 
 kdisaggSUB5
Value: 2.0E-9
Constant
 
 kproteff
Value: 1.0