KEGG   PATHWAY: mcc05012Help
Entry
mcc05012                    Pathway                                

Name
Parkinson's disease - Macaca mulatta (rhesus monkey)
Description
Parkinson's disease (PD) is a progressive neurodegenerative movement disorder that results primarily from the death of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc). Mutations in alpha-synuclein, UCHL1 (a ubiquitin carboxy-terminal hydrolase L1), parkin, DJ1 (a parkin-associated protein involved with oxidative stress), and PINK1 (a putative serine threonine kinase) are known to cause early-onset PD. Mutations or altered expression of these proteins contributes to the damage and subsequent loss of DA neurons through common mechanisms that result in proteasome dysfunction, mitochondrial impairment, and oxidative stress. The demise of DA neurons located in the SNc leads to a drop in the dopaminergic input to the striatum. This results in a reduced activation of the direct pathway and in a disinhibition of the indirect pathway, which is associated with the elevation of adenosine A2A receptor transmission. Such unbalanced activity of the striatal output pathway is at the basis of the motor impairment observed in PD.
Class
Human Diseases; Neurodegenerative diseases
BRITE hierarchy
Pathway map
Parkinson's disease
mcc05012

All organismsOrtholog table
Organism
Macaca mulatta (rhesus monkey) [GN:mcc]
Gene
707865  
ADORA2A; adenosine A2a receptor [KO:K04266]
694181  
DRD2; dopamine receptor D2 [KO:K04145]
699310  
GNAI3; guanine nucleotide binding protein (G protein), alpha inhibiting activity polypeptide 3 [KO:K04630]
703780  
GNAI2; guanine nucleotide binding protein (G protein), alpha inhibiting activity polypeptide 2 [KO:K04630]
708940  
GNAI1; guanine nucleotide binding protein (G protein), alpha inhibiting activity polypeptide 1 [KO:K04630]
715897  
ADCY5; adenylate cyclase 5 [KO:K08045] [EC:4.6.1.1]
709728  
PRKACB; protein kinase, cAMP-dependent, beta catalytic subunit [KO:K04345] [EC:2.7.11.11]
718632  
PRKACA; protein kinase, cAMP-dependent, alpha catalytic subunit [KO:K04345] [EC:2.7.11.11]
700652  
PRKACG; protein kinase, cAMP-dependent, gamma catalytic subunit [KO:K04345] [EC:2.7.11.11]
697796  
DRD1; dopamine receptor D1 [KO:K04144]
706324  
UBA1; ubiquitin-like modifier activating enzyme 1 [KO:K03178] [EC:6.2.1.45]
704875  
UBA7; ubiquitin-like modifier activating enzyme 7 [KO:K10698] [EC:6.2.1.45]
696110  
UBB; ubiquitin B [KO:K04551]
699895  
UBE2L3; ubiquitin-conjugating enzyme E2 L3 [KO:K04552] [EC:2.3.2.23]
697675  
UBE2L3; ubiquitin conjugating enzyme E2L 3 [KO:K04552] [EC:2.3.2.23]
705561  
UBE2L6; ubiquitin conjugating enzyme E2L 6 [KO:K04553] [EC:2.3.2.23]
700798  
UBE2J2; ubiquitin conjugating enzyme E2, J2 [KO:K04554] [EC:2.3.2.23]
701100  
UBE2J1; ubiquitin conjugating enzyme E2, J1 [KO:K10578] [EC:2.3.2.23]
710862  
UBE2G2; ubiquitin conjugating enzyme E2G 2 [KO:K04555] [EC:2.3.2.23]
721528  
UBE2G1; ubiquitin conjugating enzyme E2G 1 [KO:K10575] [EC:2.3.2.23]
710899  
PARK2; parkin RBR E3 ubiquitin protein ligase [KO:K04556] [EC:2.3.2.27]
706985  
SNCA; synuclein alpha [KO:K04528]
696628  
GPR37; G protein-coupled receptor 37 (endothelin receptor type B-like) [KO:K04243]
712041  
SEPT5; septin 5 [KO:K04557]
700372  
SNCAIP; synuclein alpha interacting protein [KO:K04558]
701579  
UCHL1; ubiquitin C-terminal hydrolase L1 [KO:K05611] [EC:3.4.19.12]
721137  
TH; tyrosine hydroxylase [KO:K00501] [EC:1.14.16.2]
574143  
SLC6A3; solute carrier family 6 (neurotransmitter transporter), member 3 [KO:K05036]
701133  
SLC18A2; solute carrier family 18 (vesicular monoamine transporter), member 2 [KO:K08155]
705489  
SLC18A1; solute carrier family 18 (vesicular monoamine transporter), member 1 [KO:K08155]
ND1; NADH dehydrogenase subunit 1 [KO:K03878] [EC:1.6.5.3]
ND2; NADH dehydrogenase subunit 2 [KO:K03879] [EC:1.6.5.3]
ND3; NADH dehydrogenase subunit 3 [KO:K03880] [EC:1.6.5.3]
ND4; NADH dehydrogenase subunit 4 [KO:K03881] [EC:1.6.5.3]
ND4L; NADH dehydrogenase subunit 4L [KO:K03882] [EC:1.6.5.3]
ND5; NADH dehydrogenase subunit 5 [KO:K03883] [EC:1.6.5.3]
ND6; NADH dehydrogenase subunit 6 [KO:K03884] [EC:1.6.5.3]
711412  
NDUFV1; NADH:ubiquinone oxidoreductase core subunit V1 [KO:K03942] [EC:1.6.99.3 1.6.5.3]
706067  
NDUFV2; NADH:ubiquinone oxidoreductase core subunit V2 [KO:K03943] [EC:1.6.99.3 1.6.5.3]
694635  
NDUFA1; NADH:ubiquinone oxidoreductase subunit A1 [KO:K03945]
697736  
NDUFA2; NADH:ubiquinone oxidoreductase subunit A2 [KO:K03946]
705004  
NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 3; K03947 NADH dehydrogenase (ubiquinone) 1 alpha subcomplex subunit 3 [KO:K03947]
cytochrome c oxidase subunit NDUFA4; K03948 NADH dehydrogenase (ubiquinone) 1 alpha subcomplex subunit 4 [KO:K03948]
641333  
NDUFA4; NDUFA4, mitochondrial complex associated [KO:K03948]
714483  
NDUFA4L2; NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 4-like 2 [KO:K03948]
695066  
NDUFA5; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 5 [KO:K03949]
694520  
NDUFA5; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 5 [KO:K03949]
NDUFA5; NADH:ubiquinone oxidoreductase subunit A5 [KO:K03949]
709640  
NDUFA6; NADH:ubiquinone oxidoreductase subunit A6 [KO:K03950]
711212  
NDUFA7; NADH:ubiquinone oxidoreductase subunit A7 [KO:K03951]
698706  
NDUFA8; NADH:ubiquinone oxidoreductase subunit A8 [KO:K03952]
721906  
NDUFA9; NADH:ubiquinone oxidoreductase subunit A9 [KO:K03953]
697681  
NDUFA10; NADH:ubiquinone oxidoreductase subunit A10 [KO:K03954]
700718  
NDUFAB1; NADH:ubiquinone oxidoreductase subunit AB1 [KO:K03955]
697843  
NDUFA11; NADH:ubiquinone oxidoreductase subunit A11 [KO:K03956]
711970  
NDUFA12; NADH:ubiquinone oxidoreductase subunit A12 [KO:K11352]
716666  
NDUFA13; NADH:ubiquinone oxidoreductase subunit A13 [KO:K11353]
697745  
NDUFB1; NADH:ubiquinone oxidoreductase subunit B1 [KO:K03957]
693431  
NDUFB2; NADH:ubiquinone oxidoreductase subunit B2 [KO:K03958]
700944  
NDUFB3; NADH:ubiquinone oxidoreductase subunit B3 [KO:K03959]
694795  
NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 3-like; K03959 NADH dehydrogenase (ubiquinone) 1 beta subcomplex subunit 3 [KO:K03959]
713428  
NDUFB4; NADH:ubiquinone oxidoreductase subunit B4 [KO:K03960]
708821  
NDUFB5; NADH:ubiquinone oxidoreductase subunit B5 [KO:K03961]
704867  
NDUFB6; NADH:ubiquinone oxidoreductase subunit B6 [KO:K03962]
717849  
NDUFB7; NADH:ubiquinone oxidoreductase subunit B7 [KO:K03963]
710521  
NDUFB8; NADH:ubiquinone oxidoreductase subunit B8 [KO:K03964]
718711  
NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 8; K03964 NADH dehydrogenase (ubiquinone) 1 beta subcomplex subunit 8 [KO:K03964]
711387  
NDUFB9; NADH:ubiquinone oxidoreductase subunit B9 [KO:K03965]
693482  
NDUFB10; NADH:ubiquinone oxidoreductase subunit B10 [KO:K03966]
705984  
NDUFB11; NADH:ubiquinone oxidoreductase subunit B11 [KO:K11351]
706912  
NDUFS1; NADH:ubiquinone oxidoreductase core subunit S1 [KO:K03934] [EC:1.6.99.3 1.6.5.3]
719935  
NDUFS2; NADH:ubiquinone oxidoreductase core subunit S2 [KO:K03935] [EC:1.6.99.3 1.6.5.3]
713040  
NDUFS3; NADH:ubiquinone oxidoreductase core subunit S3 [KO:K03936] [EC:1.6.99.3 1.6.5.3]
704137  
NDUFS4; NADH:ubiquinone oxidoreductase subunit S4 [KO:K03937]
693506  
NDUFS5; NADH dehydrogenase [ubiquinone] iron-sulfur protein 5 [KO:K03938]
709426  
NDUFS6; NADH:ubiquinone oxidoreductase subunit S6 [KO:K03939]
721259  
NDUFS7; NADH:ubiquinone oxidoreductase core subunit S7 [KO:K03940] [EC:1.6.99.3 1.6.5.3]
710845  
NDUFS8; NADH:ubiquinone oxidoreductase core subunit S8 [KO:K03941] [EC:1.6.99.3 1.6.5.3]
697242  
NDUFC1; NADH:ubiquinone oxidoreductase subunit C1 [KO:K03967]
NDUFC2; NADH:ubiquinone oxidoreductase subunit C2 [KO:K03968]
708018  
SDHA; succinate dehydrogenase complex subunit A, flavoprotein (Fp) [KO:K00234] [EC:1.3.5.1]
699810  
SDHB; succinate dehydrogenase complex subunit B, iron sulfur (Ip) [KO:K00235] [EC:1.3.5.1]
702309  
succinate dehydrogenase cytochrome b560 subunit; K00236 succinate dehydrogenase (ubiquinone) cytochrome b560 subunit [KO:K00236]
719978  
SDHC; succinate dehydrogenase complex, subunit C, integral membrane protein, 15kDa [KO:K00236]
704336  
succinate dehydrogenase cytochrome b560 subunit; K00236 succinate dehydrogenase (ubiquinone) cytochrome b560 subunit [KO:K00236]
701966  
succinate dehydrogenase cytochrome b560 subunit; K00236 succinate dehydrogenase (ubiquinone) cytochrome b560 subunit [KO:K00236]
711326  
SDHD; succinate dehydrogenase complex, subunit D, integral membrane protein [KO:K00237]
SDHD; succinate dehydrogenase complex subunit D, integral membrane protein [KO:K00237]
705178  
UQCRFS1; cytochrome b-c1 complex subunit Rieske, mitochondrial [KO:K00411] [EC:1.10.2.2]
CYTB; cytochrome b [KO:K00412]
700518  
CYC1; cytochrome c-1 [KO:K00413]
677864  
UQCRC1; ubiquinol-cytochrome c reductase core protein I [KO:K00414]
697967  
UQCRC2; ubiquinol-cytochrome c reductase core protein II [KO:K00415]
707968  
UQCRH; ubiquinol-cytochrome c reductase hinge protein [KO:K00416]
701223  
UQCRB; cytochrome b-c1 complex subunit 7 [KO:K00417]
708950  
UQCRQ; ubiquinol-cytochrome c reductase, complex III subunit VII, 9.5kDa [KO:K00418]
720636  
cytochrome b-c1 complex subunit 9; K00419 ubiquinol-cytochrome c reductase subunit 9 [KO:K00419]
708396  
UQCR; ubiquinol-cytochrome c reductase, 6.4kDa subunit [KO:K00420]
COX3; cytochrome c oxidase subunit III [KO:K02262]
COX1; cytochrome c oxidase subunit I [KO:K02256] [EC:1.9.3.1]
COX2; cytochrome c oxidase subunit II [KO:K02261]
693811  
COX4I1; cytochrome c oxidase subunit IV isoform 1 [KO:K02263]
713095  
COX4I2; cytochrome c oxidase subunit IV isoform 2 (lung) [KO:K02263]
692061  
COX5A; cytochrome c oxidase subunit 5A [KO:K02264]
701661  
cytochrome c oxidase subunit 5B; K02265 cytochrome c oxidase subunit 5b [KO:K02265]
707227  
cytochrome c oxidase subunit 5B; K02265 cytochrome c oxidase subunit 5b [KO:K02265]
713995  
COX6A2; cytochrome c oxidase subunit VIa polypeptide 2 [KO:K02266]
696956  
cytochrome c oxidase subunit 6A1; K02266 cytochrome c oxidase subunit 6a [KO:K02266]
COX6B2; cytochrome c oxidase subunit 6B2 [KO:K02267]
692062  
COX6B1; cytochrome c oxidase subunit 6B [KO:K02267]
703685  
cytochrome c oxidase subunit 6C; K02268 cytochrome c oxidase subunit 6c [KO:K02268]
692060  
COX7AH; cytochrome c oxidase subunit 7AH [KO:K02270]
712764  
COX7A2L; cytochrome c oxidase subunit VIIa polypeptide 2 like [KO:K02270]
cytochrome c oxidase subunit 7A-related protein; K02270 cytochrome c oxidase subunit 7a [KO:K02270]
717879  
COX7A2; cytochrome c oxidase subunit 7A2, mitochondrial [KO:K02270]
706099  
COX7B; cytochrome c oxidase subunit VIIb [KO:K02271]
COX7B2; cytochrome c oxidase subunit VIIb2 [KO:K02271]
COX7C; cytochrome c oxidase subunit VIIc [KO:K02272]
718007  
COX8A; cytochrome c oxidase subunit VIIIA (ubiquitous) [KO:K02273]
701389  
ATP5A1; ATP synthase, H+ transporting, mitochondrial F1 complex, alpha subunit 1, cardiac muscle [KO:K02132]
713284  
ATP5B; ATP synthase, H+ transporting, mitochondrial F1 complex, beta polypeptide [KO:K02133] [EC:3.6.3.14]
713768  
ATP5C1; ATP synthase, H+ transporting, mitochondrial F1 complex, gamma polypeptide 1 [KO:K02136]
705944  
ATP5D; ATP synthase, H+ transporting, mitochondrial F1 complex, delta subunit [KO:K02134]
574260  
ATP5E; ATP synthase, H+ transporting, mitochondrial F1 complex, epsilon subunit [KO:K02135]
ATP6; ATP synthase F0 subunit 6 [KO:K02126]
704072  
ATP5F1; ATP synthase, H+ transporting, mitochondrial Fo complex subunit B1 [KO:K02127]
711417  
ATP synthase; K02128 F-type H+-transporting ATPase subunit c [KO:K02128]
706691  
ATP synthase; K02128 F-type H+-transporting ATPase subunit c [KO:K02128]
697950  
ATP5G1; ATP synthase, H+ transporting, mitochondrial Fo complex subunit C1 (subunit 9) [KO:K02128]
703751  
ATP5G2; ATP synthase, H+ transporting, mitochondrial Fo complex subunit C2 (subunit 9) [KO:K02128]
707476  
ATP synthase; K02128 F-type H+-transporting ATPase subunit c [KO:K02128]
696144  
ATP synthase; K02128 F-type H+-transporting ATPase subunit c [KO:K02128]
700815  
ATP synthase; K02128 F-type H+-transporting ATPase subunit c [KO:K02128]
694260  
ATP synthase; K02128 F-type H+-transporting ATPase subunit c [KO:K02128]
702893  
ATP5G3; ATP synthase, H+ transporting, mitochondrial Fo complex subunit C3 (subunit 9) [KO:K02128]
700338  
ATP5H; ATP synthase, H+ transporting, mitochondrial Fo complex subunit D [KO:K02138]
699117  
ATP synthase subunit d; K02138 F-type H+-transporting ATPase subunit d [KO:K02138]
698480  
ATP5O; ATP synthase, H+ transporting, mitochondrial F1 complex, O subunit [KO:K02137]
708411  
ATP5J; ATP synthase, H+ transporting, mitochondrial Fo complex subunit F6 [KO:K02131]
ATP8; ATP synthase F0 subunit 8 [KO:K02125]
697930  
LRRK2; leucine-rich repeat kinase 2 [KO:K08844] [EC:2.7.11.1]
698013  
serine/threonine-protein kinase PINK1; K05688 PTEN induced putative kinase 1 [EC:2.7.11.1] [KO:K05688] [EC:2.7.11.1]
706037  
PINK1; PTEN induced putative kinase 1 [KO:K05688] [EC:2.7.11.1]
708377  
PARK7; parkinson protein 7 [KO:K05687]
709938  
HTRA2; HtrA serine peptidase 2 [KO:K08669] [EC:3.4.21.108]
710045  
VDAC1; voltage-dependent anion channel 1 [KO:K05862]
704257  
VDAC2; voltage-dependent anion channel 2 [KO:K15040]
705116  
VDAC3; voltage-dependent anion channel 3 [KO:K15041]
695102  
SLC25A4; solute carrier family 25 (mitochondrial carrier [KO:K05863]
710042  
SLC25A31; solute carrier family 25 (mitochondrial carrier [KO:K05863]
719811  
SLC25A6; solute carrier family 25 (mitochondrial carrier [KO:K05863]
693502  
SLC25A5; solute carrier family 25 (mitochondrial carrier [KO:K05863]
574137  
PPIF; peptidylprolyl isomerase F [KO:K09565] [EC:5.2.1.8]
705449  
cytochrome c-like; K08738 cytochrome c [KO:K08738]
716056  
cytochrome c-like; K08738 cytochrome c [KO:K08738]
711309  
cytochrome c-like; K08738 cytochrome c [KO:K08738]
698225  
cytochrome c-like; K08738 cytochrome c [KO:K08738]
701246  
cytochrome c-like; K08738 cytochrome c [KO:K08738]
699951  
cytochrome c-like; K08738 cytochrome c [KO:K08738]
702488  
cytochrome c-like; K08738 cytochrome c [KO:K08738]
CYCS; cytochrome c, somatic [KO:K08738]
CYCS; cytochrome c [KO:K08738]
694164  
APAF1; apoptotic peptidase activating factor 1 [KO:K02084]
694544  
CASP9; caspase 9 [KO:K04399] [EC:3.4.22.62]
694473  
CASP3; caspase 3 [KO:K02187] [EC:3.4.22.56]
Compound
C00002  
ATP
C00008  
ADP
C00009  
Orthophosphate
C00013  
Diphosphate
C00020  
AMP
C00027  
Hydrogen peroxide
C00082  
L-Tyrosine
C00212  
Adenosine
C00355  
3,4-Dihydroxy-L-phenylalanine
C00575  
3',5'-Cyclic AMP
C00704  
O2.-
C03758  
Dopamine
C04599  
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
C07593  
Rotenone
C11310  
1-Methyl-4-phenylpyridinium
Reference
  Authors
Thomas B, Beal MF
  Title
Parkinson's disease.
  Journal
Hum Mol Genet 16 Spec No. 2:R183-94 (2007)
Reference
  Authors
Lim KL, Lim TM
  Title
Molecular mechanisms of neurodegeneration in Parkinson's disease: clues from Mendelian syndromes.
  Journal
IUBMB Life 55:315-22 (2003)
Reference
  Authors
Moore DJ, West AB, Dawson VL, Dawson TM
  Title
Molecular pathophysiology of Parkinson's disease.
  Journal
Annu Rev Neurosci 28:57-87 (2005)
Reference
  Authors
Abou-Sleiman PM, Muqit MM, Wood NW
  Title
Expanding insights of mitochondrial dysfunction in Parkinson's disease.
  Journal
Nat Rev Neurosci 7:207-19 (2006)
Reference
  Authors
Mizuno Y, Hattori N, Kubo S, Sato S, Nishioka K, Hatano T, Tomiyama H, Funayama M, Machida Y, Mochizuki H
  Title
Progress in the pathogenesis and genetics of Parkinson's disease.
  Journal
Philos Trans R Soc Lond B Biol Sci 363:2215-27 (2008)
Reference
  Authors
Gandhi S, Wood NW
  Title
Molecular pathogenesis of Parkinson's disease.
  Journal
Hum Mol Genet 14 Spec No. 2:2749-2755 (2005)
Reference
  Authors
Lotharius J, Brundin P
  Title
Pathogenesis of Parkinson's disease: dopamine, vesicles and alpha-synuclein.
  Journal
Nat Rev Neurosci 3:932-42 (2002)
Reference
  Authors
Eriksen JL, Wszolek Z, Petrucelli L
  Title
Molecular pathogenesis of Parkinson disease.
  Journal
Arch Neurol 62:353-7 (2005)
Reference
  Authors
Sidhu A, Wersinger C, Vernier P
  Title
Does alpha-synuclein modulate dopaminergic synaptic content and tone at the synapse?
  Journal
FASEB J 18:637-47 (2004)
Reference
  Authors
Sidhu A, Wersinger C, Moussa CE, Vernier P
  Title
The role of alpha-synuclein in both neuroprotection and neurodegeneration.
  Journal
Ann N Y Acad Sci 1035:250-70 (2004)
Reference
  Authors
Dauer W, Przedborski S
  Title
Parkinson's disease: mechanisms and models.
  Journal
Neuron 39:889-909 (2003)
Reference
  Authors
Feany MB
  Title
New genetic insights into Parkinson's disease.
  Journal
N Engl J Med 351:1937-40 (2004)
Reference
  Authors
Beal MF
  Title
Experimental models of Parkinson's disease.
  Journal
Nat Rev Neurosci 2:325-34 (2001)
Reference
  Authors
Corti O, Hampe C, Darios F, Ibanez P, Ruberg M, Brice A
  Title
Parkinson's disease: from causes to mechanisms.
  Journal
C R Biol 328:131-42 (2005)
Reference
  Authors
Vila M, Ramonet D, Perier C
  Title
Mitochondrial alterations in Parkinson's disease: new clues.
  Journal
J Neurochem 107:317-28 (2008)
Reference
  Authors
Vila M, Przedborski S
  Title
Targeting programmed cell death in neurodegenerative diseases.
  Journal
Nat Rev Neurosci 4:365-75 (2003)
Reference
  Authors
Calabresi P, Di Filippo M, Gallina A, Wang Y, Stankowski JN, Picconi B, Dawson VL, Dawson TM
  Title
New synaptic and molecular targets for neuroprotection in Parkinson's disease.
  Journal
Mov Disord 28:51-60 (2013)
Reference
  Authors
Nishi A, Kuroiwa M, Shuto T
  Title
Mechanisms for the modulation of dopamine d(1) receptor signaling in striatal neurons.
  Journal
Front Neuroanat 5:43 (2011)
Reference
  Authors
Hara M, Fukui R, Hieda E, Kuroiwa M, Bateup HS, Kano T, Greengard P, Nishi A
  Title
Role of adrenoceptors in the regulation of dopamine/DARPP-32 signaling in neostriatal neurons.
  Journal
J Neurochem 113:1046-59 (2010)
KO pathway
 

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