KEGG   PATHWAY: hsa05012Help
Entry
hsa05012                    Pathway                                

Name
Parkinson's disease - Homo sapiens (human)
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
hsa05012

All organismsOrtholog table
Disease
H00057  
Parkinson's disease (PD)
Drug
D04641  
Istradefylline (JAN/USAN/INN)
D07836  
Dihydroergocryptine mesilate
D10014  
Ioflupane I 123 (USAN)
Organism
Homo sapiens (human) [GN:hsa]
Gene
135  
ADORA2A; adenosine A2a receptor [KO:K04266]
2774  
GNAL; G protein subunit alpha L [KO:K04633]
1813  
DRD2; dopamine receptor D2 [KO:K04145]
2770  
GNAI1; G protein subunit alpha i1 [KO:K04630]
2773  
GNAI3; G protein subunit alpha i3 [KO:K04630]
2771  
GNAI2; G protein subunit alpha i2 [KO:K04630]
111  
ADCY5; adenylate cyclase 5 [KO:K08045] [EC:4.6.1.1]
5566  
PRKACA; protein kinase cAMP-activated catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
5567  
PRKACB; protein kinase cAMP-activated catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
5568  
PRKACG; protein kinase cAMP-activated catalytic subunit gamma [KO:K04345] [EC:2.7.11.11]
1812  
DRD1; dopamine receptor D1 [KO:K04144]
7317  
UBA1; ubiquitin like modifier activating enzyme 1 [KO:K03178] [EC:6.2.1.45]
7318  
UBA7; ubiquitin like modifier activating enzyme 7 [KO:K10698] [EC:6.2.1.45]
7314  
UBB; ubiquitin B [KO:K04551]
7332  
UBE2L3; ubiquitin conjugating enzyme E2 L3 [KO:K04552] [EC:2.3.2.23]
9246  
UBE2L6; ubiquitin conjugating enzyme E2 L6 [KO:K04553] [EC:2.3.2.23]
118424  
UBE2J2; ubiquitin conjugating enzyme E2 J2 [KO:K04554] [EC:2.3.2.23]
51465  
UBE2J1; ubiquitin conjugating enzyme E2 J1 [KO:K10578] [EC:2.3.2.23]
7327  
UBE2G2; ubiquitin conjugating enzyme E2 G2 [KO:K04555] [EC:2.3.2.23]
7326  
UBE2G1; ubiquitin conjugating enzyme E2 G1 [KO:K10575] [EC:2.3.2.23]
5071  
PARK2; parkin RBR E3 ubiquitin protein ligase [KO:K04556] [EC:2.3.2.27]
6622  
SNCA; synuclein alpha [KO:K04528]
2861  
GPR37; G protein-coupled receptor 37 [KO:K04243]
5413  
SEPT5; septin 5 [KO:K04557]
9627  
SNCAIP; synuclein alpha interacting protein [KO:K04558]
7345  
UCHL1; ubiquitin C-terminal hydrolase L1 [KO:K05611] [EC:3.4.19.12]
7054  
TH; tyrosine hydroxylase [KO:K00501] [EC:1.14.16.2]
6531  
SLC6A3; solute carrier family 6 member 3 [KO:K05036]
6570  
SLC18A1; solute carrier family 18 member A1 [KO:K08155]
6571  
SLC18A2; solute carrier family 18 member A2 [KO:K08155]
4535  
ND1; NADH dehydrogenase, subunit 1 (complex I) [KO:K03878] [EC:1.6.5.3]
4536  
ND2; MTND2 [KO:K03879] [EC:1.6.5.3]
4537  
ND3; NADH dehydrogenase, subunit 3 (complex I) [KO:K03880] [EC:1.6.5.3]
4538  
ND4; NADH dehydrogenase, subunit 4 (complex I) [KO:K03881] [EC:1.6.5.3]
4539  
ND4L; NADH dehydrogenase, subunit 4L (complex I) [KO:K03882] [EC:1.6.5.3]
4540  
ND5; NADH dehydrogenase, subunit 5 (complex I) [KO:K03883] [EC:1.6.5.3]
4541  
ND6; NADH dehydrogenase, subunit 6 (complex I) [KO:K03884] [EC:1.6.5.3]
4723  
NDUFV1; NADH:ubiquinone oxidoreductase core subunit V1 [KO:K03942] [EC:1.6.99.3 1.6.5.3]
4729  
NDUFV2; NADH:ubiquinone oxidoreductase core subunit V2 [KO:K03943] [EC:1.6.99.3 1.6.5.3]
4731  
NDUFV3; NADH:ubiquinone oxidoreductase subunit V3 [KO:K03944]
4694  
NDUFA1; NADH:ubiquinone oxidoreductase subunit A1 [KO:K03945]
4695  
NDUFA2; NADH:ubiquinone oxidoreductase subunit A2 [KO:K03946]
4696  
NDUFA3; NADH:ubiquinone oxidoreductase subunit A3 [KO:K03947]
4697  
NDUFA4; NDUFA4, mitochondrial complex associated [KO:K03948]
56901  
NDUFA4L2; NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 4-like 2 [KO:K03948]
4698  
NDUFA5; NADH:ubiquinone oxidoreductase subunit A5 [KO:K03949]
4700  
NDUFA6; NADH:ubiquinone oxidoreductase subunit A6 [KO:K03950]
4701  
NDUFA7; NADH:ubiquinone oxidoreductase subunit A7 [KO:K03951]
4702  
NDUFA8; NADH:ubiquinone oxidoreductase subunit A8 [KO:K03952]
4704  
NDUFA9; NADH:ubiquinone oxidoreductase subunit A9 [KO:K03953]
4705  
NDUFA10; NADH:ubiquinone oxidoreductase subunit A10 [KO:K03954]
4706  
NDUFAB1; NADH:ubiquinone oxidoreductase subunit AB1 [KO:K03955]
126328  
NDUFA11; NADH:ubiquinone oxidoreductase subunit A11 [KO:K03956]
55967  
NDUFA12; NADH:ubiquinone oxidoreductase subunit A12 [KO:K11352]
51079  
NDUFA13; NADH:ubiquinone oxidoreductase subunit A13 [KO:K11353]
4707  
NDUFB1; NADH:ubiquinone oxidoreductase subunit B1 [KO:K03957]
4708  
NDUFB2; NADH:ubiquinone oxidoreductase subunit B2 [KO:K03958]
4709  
NDUFB3; NADH:ubiquinone oxidoreductase subunit B3 [KO:K03959]
4710  
NDUFB4; NADH:ubiquinone oxidoreductase subunit B4 [KO:K03960]
4711  
NDUFB5; NADH:ubiquinone oxidoreductase subunit B5 [KO:K03961]
4712  
NDUFB6; NADH:ubiquinone oxidoreductase subunit B6 [KO:K03962]
4713  
NDUFB7; NADH:ubiquinone oxidoreductase subunit B7 [KO:K03963]
4714  
NDUFB8; NADH:ubiquinone oxidoreductase subunit B8 [KO:K03964]
4715  
NDUFB9; NADH:ubiquinone oxidoreductase subunit B9 [KO:K03965]
4716  
NDUFB10; NADH:ubiquinone oxidoreductase subunit B10 [KO:K03966]
54539  
NDUFB11; NADH:ubiquinone oxidoreductase subunit B11 [KO:K11351]
4719  
NDUFS1; NADH:ubiquinone oxidoreductase core subunit S1 [KO:K03934] [EC:1.6.99.3 1.6.5.3]
4720  
NDUFS2; NADH:ubiquinone oxidoreductase core subunit S2 [KO:K03935] [EC:1.6.99.3 1.6.5.3]
4722  
NDUFS3; NADH:ubiquinone oxidoreductase core subunit S3 [KO:K03936] [EC:1.6.99.3 1.6.5.3]
4724  
NDUFS4; NADH:ubiquinone oxidoreductase subunit S4 [KO:K03937]
4725  
NDUFS5; NADH:ubiquinone oxidoreductase subunit S5 [KO:K03938]
4726  
NDUFS6; NADH:ubiquinone oxidoreductase subunit S6 [KO:K03939]
374291  
NDUFS7; NADH:ubiquinone oxidoreductase core subunit S7 [KO:K03940] [EC:1.6.99.3 1.6.5.3]
4728  
NDUFS8; NADH:ubiquinone oxidoreductase core subunit S8 [KO:K03941] [EC:1.6.99.3 1.6.5.3]
4717  
NDUFC1; NADH:ubiquinone oxidoreductase subunit C1 [KO:K03967]
4718  
NDUFC2; NADH:ubiquinone oxidoreductase subunit C2 [KO:K03968]
NDUFC2-KCTD14; NDUFC2-KCTD14 readthrough [KO:K03968]
6389  
SDHA; succinate dehydrogenase complex flavoprotein subunit A [KO:K00234] [EC:1.3.5.1]
6390  
SDHB; succinate dehydrogenase complex iron sulfur subunit B [KO:K00235] [EC:1.3.5.1]
6391  
SDHC; succinate dehydrogenase complex subunit C [KO:K00236]
6392  
SDHD; succinate dehydrogenase complex subunit D [KO:K00237]
7386  
UQCRFS1; ubiquinol-cytochrome c reductase, Rieske iron-sulfur polypeptide 1 [KO:K00411] [EC:1.10.2.2]
4519  
CYTB; cytochrome b [KO:K00412]
1537  
CYC1; cytochrome c1 [KO:K00413]
7384  
UQCRC1; ubiquinol-cytochrome c reductase core protein I [KO:K00414]
7385  
UQCRC2; ubiquinol-cytochrome c reductase core protein II [KO:K00415]
7388  
UQCRH; ubiquinol-cytochrome c reductase hinge protein [KO:K00416]
440567  
UQCRHL; ubiquinol-cytochrome c reductase hinge protein like [KO:K00416]
7381  
UQCRB; ubiquinol-cytochrome c reductase binding protein [KO:K00417]
27089  
UQCRQ; ubiquinol-cytochrome c reductase complex III subunit VII [KO:K00418]
29796  
UQCR10; ubiquinol-cytochrome c reductase, complex III subunit X [KO:K00419]
10975  
UQCR11; ubiquinol-cytochrome c reductase, complex III subunit XI [KO:K00420]
4514  
COX3; cytochrome c oxidase III [KO:K02262]
4512  
COX1; cytochrome c oxidase subunit I [KO:K02256] [EC:1.9.3.1]
4513  
COX2; cytochrome c oxidase subunit II [KO:K02261]
84701  
COX4I2; cytochrome c oxidase subunit 4I2 [KO:K02263]
1327  
COX4I1; cytochrome c oxidase subunit 4I1 [KO:K02263]
9377  
COX5A; cytochrome c oxidase subunit 5A [KO:K02264]
1329  
COX5B; cytochrome c oxidase subunit 5B [KO:K02265]
1337  
COX6A1; cytochrome c oxidase subunit 6A1 [KO:K02266]
1339  
COX6A2; cytochrome c oxidase subunit 6A2 [KO:K02266]
1340  
COX6B1; cytochrome c oxidase subunit 6B1 [KO:K02267]
125965  
COX6B2; cytochrome c oxidase subunit 6B2 [KO:K02267]
1345  
COX6C; cytochrome c oxidase subunit 6C [KO:K02268]
1346  
COX7A1; cytochrome c oxidase subunit 7A1 [KO:K02270]
1347  
COX7A2; cytochrome c oxidase subunit 7A2 [KO:K02270]
9167  
COX7A2L; cytochrome c oxidase subunit 7A2 like [KO:K02270]
1349  
COX7B; cytochrome c oxidase subunit 7B [KO:K02271]
170712  
COX7B2; cytochrome c oxidase subunit 7B2 [KO:K02271]
1350  
COX7C; cytochrome c oxidase subunit 7C [KO:K02272]
341947  
COX8C; cytochrome c oxidase subunit 8C [KO:K02273]
1351  
COX8A; cytochrome c oxidase subunit 8A [KO:K02273]
498  
ATP5A1; ATP synthase, H+ transporting, mitochondrial F1 complex, alpha subunit 1, cardiac muscle [KO:K02132]
506  
ATP5B; ATP synthase, H+ transporting, mitochondrial F1 complex, beta polypeptide [KO:K02133] [EC:3.6.3.14]
509  
ATP5C1; ATP synthase, H+ transporting, mitochondrial F1 complex, gamma polypeptide 1 [KO:K02136]
513  
ATP5D; ATP synthase, H+ transporting, mitochondrial F1 complex, delta subunit [KO:K02134]
514  
ATP5E; ATP synthase, H+ transporting, mitochondrial F1 complex, epsilon subunit [KO:K02135]
4508  
ATP6; ATP synthase F0 subunit 6 [KO:K02126]
515  
ATP5F1; ATP synthase, H+ transporting, mitochondrial Fo complex subunit B1 [KO:K02127]
516  
ATP5G1; ATP synthase, H+ transporting, mitochondrial Fo complex subunit C1 (subunit 9) [KO:K02128]
517  
ATP5G2; ATP synthase, H+ transporting, mitochondrial Fo complex subunit C2 (subunit 9) [KO:K02128]
518  
ATP5G3; ATP synthase, H+ transporting, mitochondrial Fo complex subunit C3 (subunit 9) [KO:K02128]
10476  
ATP5H; ATP synthase, H+ transporting, mitochondrial Fo complex subunit D [KO:K02138]
539  
ATP5O; ATP synthase, H+ transporting, mitochondrial F1 complex, O subunit [KO:K02137]
522  
ATP5J; ATP synthase, H+ transporting, mitochondrial Fo complex subunit F6 [KO:K02131]
4509  
ATP8; ATP synthase F0 subunit 8 [KO:K02125]
120892  
LRRK2; leucine-rich repeat kinase 2 [KO:K08844] [EC:2.7.11.1]
65018  
PINK1; PTEN induced putative kinase 1 [KO:K05688] [EC:2.7.11.1]
11315  
PARK7; Parkinsonism associated deglycase [KO:K05687]
27429  
HTRA2; HtrA serine peptidase 2 [KO:K08669] [EC:3.4.21.108]
7416  
VDAC1; voltage dependent anion channel 1 [KO:K05862]
7417  
VDAC2; voltage dependent anion channel 2 [KO:K15040]
7419  
VDAC3; voltage dependent anion channel 3 [KO:K15041]
291  
SLC25A4; solute carrier family 25 member 4 [KO:K05863]
292  
SLC25A5; solute carrier family 25 member 5 [KO:K05863]
293  
SLC25A6; solute carrier family 25 member 6 [KO:K05863]
83447  
SLC25A31; solute carrier family 25 member 31 [KO:K05863]
10105  
PPIF; peptidylprolyl isomerase F [KO:K09565] [EC:5.2.1.8]
54205  
CYCS; cytochrome c, somatic [KO:K08738]
317  
APAF1; apoptotic peptidase activating factor 1 [KO:K02084]
842  
CASP9; caspase 9 [KO:K04399] [EC:3.4.22.62]
836  
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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