KEGG   PATHWAY: bta05012Help
Entry
bta05012                    Pathway                                

Name
Parkinson's disease - Bos taurus (cow)
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
bta05012

All organismsOrtholog table
Organism
Bos taurus (cow) [GN:bta]
Gene
617828  
ADORA2A; adenosine A2a receptor [KO:K04266]
GNAL; guanine nucleotide binding protein (G protein), alpha activating activity polypeptide, olfactory type [KO:K04633]
281126  
DRD2; dopamine receptor D2 [KO:K04145]
281790  
GNAI1; guanine nucleotide binding protein (G protein), alpha inhibiting activity polypeptide 1 [KO:K04630]
281791  
GNAI2; guanine nucleotide binding protein (G protein), alpha inhibiting activity polypeptide 2 [KO:K04630]
539521  
GNAI3; guanine nucleotide binding protein (G protein), alpha inhibiting activity polypeptide 3 [KO:K04630]
505740  
ADCY5; adenylate cyclase 5 [KO:K08045] [EC:4.6.1.1]
282322  
PRKACA; protein kinase, cAMP-dependent, catalytic, alpha [KO:K04345] [EC:2.7.11.11]
282323  
PRKACB; protein kinase, cAMP-dependent, catalytic, beta [KO:K04345] [EC:2.7.11.11]
505773  
PRKX; protein kinase, X-linked [KO:K04345] [EC:2.7.11.11]
281125  
DRD1; dopamine receptor D1 [KO:K04144]
282869  
UBA1; ubiquitin-like modifier activating enzyme 1 [KO:K03178] [EC:6.3.2.19]
497204  
UBA7; ubiquitin-like modifier activating enzyme 7 [KO:K10698] [EC:6.3.2.19]
281370  
UBB; ubiquitin B [KO:K04551]
767894  
UBE2L3; ubiquitin-conjugating enzyme E2L 3 [KO:K04552] [EC:6.3.2.19]
509471  
UBE2L6; ubiquitin-conjugating enzyme E2L 6 [KO:K04553] [EC:6.3.2.19]
506103  
UBE2J2; ubiquitin-conjugating enzyme E2, J2 [KO:K04554] [EC:6.3.2.19]
539754  
UBE2J1; ubiquitin-conjugating enzyme E2, J1, U [KO:K10578] [EC:6.3.2.19]
614471  
UBE2G2; ubiquitin-conjugating enzyme E2G 2 [KO:K04555] [EC:6.3.2.19]
613676  
UBE2G1; ubiquitin-conjugating enzyme E2G 1 [KO:K10575] [EC:6.3.2.19]
530858  
PARK2; parkinson protein 2, E3 ubiquitin protein ligase (parkin) [KO:K04556] [EC:6.3.2.19]
282857  
SNCA; synuclein, alpha (non A4 component of amyloid precursor) [KO:K04528]
532626  
GPR37; G protein-coupled receptor 37 (endothelin receptor type B-like) [KO:K04243]
790388  
probable G-protein coupled receptor 37-like; K04243 G protein-coupled receptor 37 (endothelin receptor type B-like) [KO:K04243]
615408  
SEPT5; septin 5 [KO:K04557]
540156  
SNCAIP; synuclein, alpha interacting protein [KO:K04558]
514394  
UCHL1; ubiquitin carboxyl-terminal esterase L1 (ubiquitin thiolesterase) [KO:K05611] [EC:3.4.19.12]
280707  
TH; tyrosine hydroxylase [KO:K00501] [EC:1.14.16.2]
788410  
SLC6A3; solute carrier family 6 (neurotransmitter transporter, dopamine), member 3 [KO:K05036]
282471  
SLC18A2; solute carrier family 18 (vesicular monoamine), member 2 [KO:K08155]
617708  
SLC18A1; solute carrier family 18 (vesicular monoamine), 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]
287014  
NDUFV1; NADH dehydrogenase (ubiquinone) flavoprotein 1, 51kDa [KO:K03942] [EC:1.6.99.3 1.6.5.3]
282290  
NDUFV2; NADH dehydrogenase (ubiquinone) flavoprotein 2, 24kDa [KO:K03943] [EC:1.6.99.3 1.6.5.3]
781824  
NDUFV2; NADH dehydrogenase [ubiquinone] flavoprotein 2, mitochondrial-like [KO:K03943] [EC:1.6.99.3 1.6.5.3]
327717  
NDUFV3; NADH dehydrogenase (ubiquinone) flavoprotein 3, 10kDa [KO:K03944]
327673  
NDUFA1; NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 1, 7.5kDa [KO:K03945]
327698  
NDUFA2; NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 2, 8kDa [KO:K03946]
338064  
NDUFA3; NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 3, 9kDa [KO:K03947]
327704  
NDUFA4; NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 4, 9kDa [KO:K03948]
613541  
NDUFA4L2; NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 4-like 2 [KO:K03948]
327714  
NDUFA5; NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 5, 13kDa [KO:K03949]
327670  
NDUFA6; NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 6, 14kDa [KO:K03950]
338063  
NDUFA7; NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 7, 14.5kDa [KO:K03951]
327710  
NDUFA8; NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 8, 19kDa [KO:K03952]
404188  
NDUFA9; NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 9, 39kDa [KO:K03953]
338060  
NDUFA10; NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 10, 42kDa [KO:K03954]
327702  
NDUFAB1; NADH dehydrogenase (ubiquinone) 1, alpha/beta subcomplex, 1, 8kDa [KO:K03955]
326346  
NDUFA11; NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 11, 14.7kDa [KO:K03956]
281742  
NDUFA12; NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 12 [KO:K11352]
338084  
NDUFA13; NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 13 [KO:K11353]
327690  
NDUFB1; NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 1, 7kDa [KO:K03957]
327713  
NDUFB2; NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 2, 8kDa [KO:K03958]
338073  
NDUFB3; NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 3, 12kDa [KO:K03959]
327706  
NDUFB4; NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 4, 15kDa [KO:K03960]
338061  
NDUFB5; NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 5, 16kDa [KO:K03961]
327665  
NDUFB6; NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 6, 17kDa [KO:K03962]
338065  
NDUFB7; NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 7, 18kDa [KO:K03963]
282517  
NDUFB8; NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 8, 19kDa [KO:K03964]
327660  
NDUFB9; NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 9, 22kDa [KO:K03965]
327701  
NDUFB10; NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 10, 22kDa [KO:K03966]
404161  
NDUFB11; NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 11, 17.3kDa [KO:K11351]
288380  
NDUFS1; NADH dehydrogenase (ubiquinone) Fe-S protein 1, 75kDa (NADH-coenzyme Q reductase) [KO:K03934] [EC:1.6.99.3 1.6.5.3]
327697  
NDUFS2; NADH dehydrogenase (ubiquinone) Fe-S protein 2, 49kDa (NADH-coenzyme Q reductase) [KO:K03935] [EC:1.6.99.3 1.6.5.3]
287327  
NDUFS3; NADH dehydrogenase (ubiquinone) Fe-S protein 3, 30kDa (NADH-coenzyme Q reductase) [KO:K03936] [EC:1.6.99.3 1.6.5.3]
327680  
NDUFS4; NADH dehydrogenase (ubiquinone) Fe-S protein 4, 18kDa (NADH-coenzyme Q reductase) [KO:K03937]
338057  
NDUFS5; NADH dehydrogenase (ubiquinone) Fe-S protein 5, 15kDa (NADH-coenzyme Q reductase) [KO:K03938]
327691  
NDUFS6; NADH dehydrogenase (ubiquinone) Fe-S protein 6, 13kDa (NADH-coenzyme Q reductase) [KO:K03939]
338079  
NDUFS7; NADH dehydrogenase (ubiquinone) Fe-S protein 7, 20kDa (NADH-coenzyme Q reductase) [KO:K03940] [EC:1.6.99.3 1.6.5.3]
287027  
NDUFS8; NADH dehydrogenase (ubiquinone) Fe-S protein 8, 23kDa (NADH-coenzyme Q reductase) [KO:K03941] [EC:1.6.99.3 1.6.5.3]
282289  
NDUFC1; NADH dehydrogenase (ubiquinone) 1, subcomplex unknown, 1, 6kDa [KO:K03967]
338046  
NDUFC2; NADH dehydrogenase (ubiquinone) 1, subcomplex unknown, 2, 14.5kDa [KO:K03968]
281480  
SDHA; succinate dehydrogenase complex, subunit A, flavoprotein (Fp) [KO:K00234] [EC:1.3.5.1]
286840  
SDHB; succinate dehydrogenase complex, subunit B, iron sulfur (Ip) [KO:K00235] [EC:1.3.5.1]
327696  
SDHC; succinate dehydrogenase complex, subunit C, integral membrane protein, 15kDa [KO:K00236]
281481  
SDHD; succinate dehydrogenase complex, subunit D, integral membrane protein [KO:K00237]
287020  
UQCRFS1; ubiquinol-cytochrome c reductase, Rieske iron-sulfur polypeptide 1 [KO:K00411] [EC:1.10.2.2]
CYTB; cytochrome b [KO:K00412]
512500  
CYC1; cytochrome c-1 [KO:K00413]
282393  
UQCRC1; ubiquinol-cytochrome c reductase core protein I [KO:K00414]
282394  
UQCRC2; ubiquinol-cytochrome c reductase core protein II [KO:K00415]
613899  
UQCRH; ubiquinol-cytochrome c reductase hinge protein [KO:K00416]
616871  
UQCRB; ubiquinol-cytochrome c reductase binding protein [KO:K00417]
286885  
UQCRQ; ubiquinol-cytochrome c reductase, complex III subunit VII, 9.5kDa [KO:K00418]
616109  
UQCR10; ubiquinol-cytochrome c reductase, complex III subunit X [KO:K00419]
281570  
UQCR11; ubiquinol-cytochrome c reductase, complex III subunit XI [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]
281090  
COX4I1; cytochrome c oxidase subunit IV isoform 1 [KO:K02263]
618339  
COX4I2; cytochrome c oxidase subunit IV isoform 2 (lung) [KO:K02263]
444878  
COX5A; cytochrome c oxidase subunit Va [KO:K02264]
287012  
COX5B; cytochrome c oxidase subunit Vb [KO:K02265]
282200  
COX6A2; cytochrome c oxidase subunit VIa polypeptide 2 [KO:K02266]
282199  
COX6A1; cytochrome c oxidase subunit VIa polypeptide 1 [KO:K02266]
cytochrome c oxidase subunit 6A1; K02266 cytochrome c oxidase subunit 6a [KO:K02266]
cytochrome c oxidase subunit 6A1; K02266 cytochrome c oxidase subunit 6a [KO:K02266]
503554  
COX6B2; cytochrome c oxidase subunit VIb polypeptide 2 (testis) [KO:K02267]
COX6B1; cytochrome c oxidase subunit VIb polypeptide 1 (ubiquitous) [KO:K02267]
614700  
MGC148714; cytochrome c oxidase subunit 6C [KO:K02268]
327688  
COX7A2; cytochrome c oxidase subunit VIIa polypeptide 2 (liver) [KO:K02270]
338086  
COX7A1; cytochrome c oxidase subunit VIIa polypeptide 1 (muscle) [KO:K02270]
540225  
COX7A2L; cytochrome c oxidase subunit VIIa polypeptide 2 like [KO:K02270]
cytochrome c oxidase subunit 7A2; K02270 cytochrome c oxidase subunit 7a [KO:K02270]
COX7B; cytochrome c oxidase subunit VIIb [KO:K02271]
767916  
COX7B2; cytochrome c oxidase subunit 7B2, mitochondrial [KO:K02271]
327718  
COX7C; cytochrome c oxidase subunit VIIc [KO:K02272]
cytochrome c oxidase subunit 7C; K02272 cytochrome c oxidase subunit 7c [KO:K02272]
281091  
COX8A; cytochrome c oxidase subunit VIIIA (ubiquitous) [KO:K02273]
783202  
cytochrome c oxidase subunit 8A; K02273 cytochrome c oxidase subunit 8 [KO:K02273]
615757  
COX8B; cytochrome c oxidase subunit VIII-H (heart/muscle) [KO:K02273]
uncharacterized LOC100300759; K02273 cytochrome c oxidase subunit 8 [KO:K02273]
282578  
ATP5A1; ATP synthase, H+ transporting, mitochondrial F1 complex, alpha subunit 1, cardiac muscle [KO:K02132]
327675  
ATP5B; ATP synthase, H+ transporting, mitochondrial F1 complex, beta polypeptide [KO:K02133] [EC:3.6.3.14]
327668  
ATP5C1; ATP synthase, H+ transporting, mitochondrial F1 complex, gamma polypeptide 1 [KO:K02136]
783991  
ATP synthase subunit gamma; K02136 F-type H+-transporting ATPase subunit gamma [KO:K02136]
338081  
ATP5D; ATP synthase, H+ transporting, mitochondrial F1 complex, delta subunit [KO:K02134]
617230  
ATP5E; ATP synthase, H+ transporting, mitochondrial F1 complex, epsilon subunit [KO:K02135]
782270  
aTP synthase; K02135 F-type H+-transporting ATPase subunit epsilon [KO:K02135]
ATP synthase subunit epsilon; K02135 F-type H+-transporting ATPase subunit epsilon [KO:K02135]
ATP synthase subunit epsilon; K02135 F-type H+-transporting ATPase subunit epsilon [KO:K02135]
ATP6; ATP synthase F0 subunit 6 [KO:K02126]
282701  
ATP5F1; ATP synthase, H+ transporting, mitochondrial Fo complex, subunit B1 [KO:K02127]
540176  
ATP5G3; ATP synthase, H+ transporting, mitochondrial Fo complex, subunit C3 (subunit 9) [KO:K02128]
337887  
ATP5G2; ATP synthase, H+ transporting, mitochondrial F0 complex, subunit C2 (subunit 9) [KO:K02128]
338053  
ATP5G1; ATP synthase, H+ transporting, mitochondrial Fo complex, subunit C1 (subunit 9) [KO:K02128]
282710  
ATP5H; ATP synthase, H+ transporting, mitochondrial Fo complex, subunit d [KO:K02138]
281640  
ATP5O; ATP synthase, H+ transporting, mitochondrial F1 complex, O subunit [KO:K02137]
282690  
ATP5J; ATP synthase, H+ transporting, mitochondrial Fo complex, subunit F6 [KO:K02131]
ATP8; ATP synthase F0 subunit 8 [KO:K02125]
535652  
LRRK2; leucine-rich repeat kinase 2 [KO:K08844] [EC:2.7.11.1]
510683  
PINK1; PTEN induced putative kinase 1 [KO:K05688] [EC:2.7.11.1]
511268  
PARK7; parkinson protein 7 [KO:K05687]
523039  
HTRA2; HtrA serine peptidase 2 [KO:K08669] [EC:3.4.21.108]
282119  
VDAC1; voltage-dependent anion channel 1 [KO:K05862]
282120  
VDAC2; voltage-dependent anion channel 2 [KO:K15040]
282716  
VDAC3; voltage-dependent anion channel 3 [KO:K15041]
282478  
SLC25A4; solute carrier family 25 (mitochondrial carrier [KO:K05863]
282479  
SLC25A5; solute carrier family 25 (mitochondrial carrier [KO:K05863]
282480  
SLC25A6; solute carrier family 25 (mitochondrial carrier [KO:K05863]
541168  
SLC25A31; solute carrier family 25 (mitochondrial carrier [KO:K05863]
787122  
ADP/ATP translocase 1-like; K05863 solute carrier family 25 (mitochondrial adenine nucleotide translocator), member 4/5/6/31 [KO:K05863]
414346  
PPIF; peptidylprolyl isomerase F [KO:K09565] [EC:5.2.1.8]
510767  
CYCS; cytochrome c, somatic [KO:K08738]
781996  
CYCT; cytochrome c, testis [KO:K08738]
cytochrome c-like; K08738 cytochrome c [KO:K08738]
537782  
APAF1; apoptotic peptidase activating factor 1 [KO:K02084]
CASP9; caspase 9, apoptosis-related cysteine peptidase [KO:K04399] [EC:3.4.22.62]
408016  
CASP3; caspase 3, apoptosis-related cysteine peptidase [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
 

DBGET integrated database retrieval system