ENTRY       hsa05012                    Pathway
NAME        Parkinson disease - Homo sapiens (human)
DESCRIPTION Parkinson 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). Both environmental factors and mutations in familial PD-linked genes such as SNCA, Parkin, DJ-1, PINK1 and LRRK2 are associated with PD pathogenesis. These pathogenic mutations and environmental factors are known to cause disease due to oxidative stress, intracellular Ca2+ homeostasis impairment, mitochondrial dysfunctions and altered protein handling compromising key roles of DA neuronal function and survival. The demise of DA neurons located in the SNc leads to a drop in the dopaminergic input to the striatum, which is hypothesized to impede movement by inducing hypo and hyper activity in striatal spiny projection neurons (SPNs) of the direct (dSPNs) and indirect (iSPNs) pathways in the basal ganglia, respectively.
CLASS       Human Diseases; Neurodegenerative disease
PATHWAY_MAP hsa05012  Parkinson disease
NETWORK     nt06410  Calcium signaling
            nt06412  Unfolded protein response (UPR) signaling
            nt06414  Apoptosis
            nt06418  Oxidative phosphorylation
            nt06419  Microtubule-based transport
            nt06420  Ubiquitin-proteasome system
            nt06421  Mitophagy
            nt06422  Dopamine metabolism
            nt06440  Transcription
            nt06460  Alzheimer disease
            nt06463  Parkinson disease
  ELEMENT   N01020  Mutation-inactivated PRKN to Parkin-mediated ubiquitination
            N01022  Mutation-inactivated PRKN to Parkin-mediated ubiquitination
            N01024  Mutation-inactivated PRKN to Parkin-mediated ubiquitination
            N01026  Mutation-inactivated PRKN to Parkin-mediated ubiquitination
            N01028  Mutation-inactivated UCHL1 to UCHL1-mediated hydrolysis
            N01030  Mutation-caused aberrant SNCA to 26S proteasome-mediated protein degradation
            N01031  Mutation-caused aberrant SNCA to VGCC-Ca2+ -apoptotic pathway
            N01032  Mutation-inactivated PRKN to mGluR1 signaling pathway
            N01033  Mutation-caused aberrant SNCA to ATF6-mediated transcription
            N01034  Mutation-caused aberrant SNCA to IRE1a-XBP1 signaling pathway
            N01035  Mutation-caused aberrant SNCA to PERK-ATF4 signaling pathway
            N01037  Mutation-caused aberrant SNCA to L-DOPA generation
            N01039  Mutation-inactivated PRKN to DOPAL generation
            N01041  Mutation-caused aberrant SNCA to transport of dopamine
            N01042  Mutation-caused aberrant SNCA to electron transfer in Complex I
            N01043  Mutation-inactivated PINK1 to electron transfer in Complex I
            N01044  MPP+ to electron transfer in Complex I
            N01045  Rotenone to electron transfer in Complex I
            N01046  Maneb to electron transfer in Complex III
            N01047  Mutation-activated LRRK2 to intrinsic apoptotic pathway
            N01048  Mutation-inactivated PINK1 to intrinsic apoptotic pathway
            N01049  Mutation-inactivated PRKN to intrinsic apoptotic pathway
            N01050  Mutation-inactivated PINK1 to intrinsic apoptotic pathway
            N01051  Mutation-inactivated DJ1 to intrinsic apoptotic pathway
            N01053  Mutation-inactivated PINK1 to PINK1-Parkin-mediated MFN2 degradation
            N01054  Mutation-inactivated PRKN to PINK1-Parkin-mediated MFN2 degradation
            N01055  Mutation-caused aberrant SNCA to anterograde axonal transport
            N01057  Mutation-inactivated DJ1 to FAS-JNK signaling patwhay
            N01058  Mutation-inactivated DJ1 to to p53-mediated transcription
            N01059  Mutation-inactivated DJ1 to KEAP1-NRF2 signaling pathway
            N01402  Manganese to electron transfer in Complex II
            N01417  Paraquat to FAS-JNK signaling pathway
DISEASE     H00057  Parkinson disease
DRUG        D00059  Levodopa (JP18/USP/INN)
            D00502  Pergolide mesylate (USP)
            D00559  Pramipexole dihydrochloride (USP)
            D00780  Bromocriptine mesylate (USP)
            D00784  Ropinirole hydrochloride (JAN/USP)
            D00987  Cabergoline (JP18/USP/INN)
            D01505  Talipexole hydrochloride (JAN)
            D02004  Apomorphine hydrochloride (USP)
            D03165  Bromocriptine (USAN/INN)
            D04641  Istradefylline (JAN/USAN/INN)
            D05575  Pramipexole (USAN/INN)
            D05768  Rotigotine (JAN/USAN/INN)
            D05804  Sarizotan hydrochloride (USAN)
            D07460  Apomorphine (BAN)
            D08339  Pergolide (INN)
            D08489  Ropinirole (USAN/INN)
            D10014  Ioflupane I 123 (USAN)
            D11420  Prasinezumab (USAN/INN)
            D11467  Cinpanemab (USAN)
ORGANISM    Homo sapiens (human) [GN:hsa]
GENE        135  ADORA2A; adenosine A2a receptor [KO:K04266]
            2774  GNAL; G protein subunit alpha L [KO:K04633]
            2778  GNAS; GNAS complex locus [KO:K04632]
            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]
            7311  UBA52; ubiquitin A-52 residue ribosomal protein fusion product 1 [KO:K02927]
            6233  RPS27A; ribosomal protein S27a [KO:K02977]
            7314  UBB; ubiquitin B [KO:K04551]
            7316  UBC; ubiquitin C [KO:K08770]
            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  PRKN; parkin RBR E3 ubiquitin protein ligase [KO:K04556] [EC:2.3.2.31]
            6622  SNCA; synuclein alpha [KO:K04528]
            2861  GPR37; G protein-coupled receptor 37 [KO:K04243]
            5413  SEPTIN5; septin 5 [KO:K04557]
            9627  SNCAIP; synuclein alpha interacting protein [KO:K04558]
            5687  PSMA6; proteasome 20S subunit alpha 6 [KO:K02730] [EC:3.4.25.1]
            5683  PSMA2; proteasome 20S subunit alpha 2 [KO:K02726] [EC:3.4.25.1]
            5685  PSMA4; proteasome 20S subunit alpha 4 [KO:K02728] [EC:3.4.25.1]
            5688  PSMA7; proteasome 20S subunit alpha 7 [KO:K02731] [EC:3.4.25.1]
            143471  PSMA8; proteasome 20S subunit alpha 8 [KO:K02731] [EC:3.4.25.1]
            5686  PSMA5; proteasome 20S subunit alpha 5 [KO:K02729] [EC:3.4.25.1]
            5682  PSMA1; proteasome 20S subunit alpha 1 [KO:K02725] [EC:3.4.25.1]
            5684  PSMA3; proteasome 20S subunit alpha 3 [KO:K02727] [EC:3.4.25.1]
            5694  PSMB6; proteasome 20S subunit beta 6 [KO:K02738] [EC:3.4.25.1]
            5695  PSMB7; proteasome 20S subunit beta 7 [KO:K02739] [EC:3.4.25.1]
            5691  PSMB3; proteasome 20S subunit beta 3 [KO:K02735] [EC:3.4.25.1]
            5690  PSMB2; proteasome 20S subunit beta 2 [KO:K02734] [EC:3.4.25.1]
            5693  PSMB5; proteasome 20S subunit beta 5 [KO:K02737] [EC:3.4.25.1]
            5689  PSMB1; proteasome 20S subunit beta 1 [KO:K02732] [EC:3.4.25.1]
            5692  PSMB4; proteasome 20S subunit beta 4 [KO:K02736] [EC:3.4.25.1]
            5701  PSMC2; proteasome 26S subunit, ATPase 2 [KO:K03061]
            5700  PSMC1; proteasome 26S subunit, ATPase 1 [KO:K03062]
            5704  PSMC4; proteasome 26S subunit, ATPase 4 [KO:K03063]
            5706  PSMC6; proteasome 26S subunit, ATPase 6 [KO:K03064]
            5702  PSMC3; proteasome 26S subunit, ATPase 3 [KO:K03065]
            5705  PSMC5; proteasome 26S subunit, ATPase 5 [KO:K03066]
            5708  PSMD2; proteasome 26S subunit ubiquitin receptor, non-ATPase 2 [KO:K03028]
            5707  PSMD1; proteasome 26S subunit, non-ATPase 1 [KO:K03032]
            5709  PSMD3; proteasome 26S subunit, non-ATPase 3 [KO:K03033]
            5715  PSMD9; proteasome 26S subunit, non-ATPase 9 [KO:K06693]
            5718  PSMD12; proteasome 26S subunit, non-ATPase 12 [KO:K03035]
            5717  PSMD11; proteasome 26S subunit, non-ATPase 11 [KO:K03036]
            9861  PSMD6; proteasome 26S subunit, non-ATPase 6 [KO:K03037]
            5713  PSMD7; proteasome 26S subunit, non-ATPase 7 [KO:K03038]
            5719  PSMD13; proteasome 26S subunit, non-ATPase 13 [KO:K03039]
            5710  PSMD4; proteasome 26S subunit ubiquitin receptor, non-ATPase 4 [KO:K03029]
            10213  PSMD14; proteasome 26S subunit, non-ATPase 14 [KO:K03030]
            5714  PSMD8; proteasome 26S subunit, non-ATPase 8 [KO:K03031]
            11047  ADRM1; ADRM1 26S proteasome ubiquitin receptor [KO:K06691]
            7979  SEM1; SEM1 26S proteasome subunit [KO:K10881]
            7345  UCHL1; ubiquitin C-terminal hydrolase L1 [KO:K05611] [EC:3.4.19.12]
            810  CALML3; calmodulin like 3 [KO:K02183]
            805  CALM2; calmodulin 2 [KO:K02183]
            808  CALM3; calmodulin 3 [KO:K02183]
            801  CALM1; calmodulin 1 [KO:K02183]
            163688  CALML6; calmodulin like 6 [KO:K02183]
            51806  CALML5; calmodulin like 5 [KO:K02183]
            91860  CALML4; calmodulin like 4 [KO:K02183]
            815  CAMK2A; calcium/calmodulin dependent protein kinase II alpha [KO:K04515] [EC:2.7.11.17]
            817  CAMK2D; calcium/calmodulin dependent protein kinase II delta [KO:K04515] [EC:2.7.11.17]
            816  CAMK2B; calcium/calmodulin dependent protein kinase II beta [KO:K04515] [EC:2.7.11.17]
            818  CAMK2G; calcium/calmodulin dependent protein kinase II gamma [KO:K04515] [EC:2.7.11.17]
            4137  MAPT; microtubule associated protein tau [KO:K04380]
            6263  RYR3; ryanodine receptor 3 [KO:K04963]
            3708  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
            3709  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
            3710  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
            5335  PLCG1; phospholipase C gamma 1 [KO:K01116] [EC:3.1.4.11]
            3309  HSPA5; heat shock protein family A (Hsp70) member 5 [KO:K09490] [EC:3.6.4.10]
            22926  ATF6; activating transcription factor 6 [KO:K09054]
            1649  DDIT3; DNA damage inducible transcript 3 [KO:K04452]
            2081  ERN1; endoplasmic reticulum to nucleus signaling 1 [KO:K08852] [EC:2.7.11.1 3.1.26.-]
            7494  XBP1; X-box binding protein 1 [KO:K09027]
            9451  EIF2AK3; eukaryotic translation initiation factor 2 alpha kinase 3 [KO:K08860] [EC:2.7.11.1]
            1965  EIF2S1; eukaryotic translation initiation factor 2 subunit alpha [KO:K03237]
            468  ATF4; activating transcription factor 4 [KO:K04374]
            7054  TH; tyrosine hydroxylase [KO:K00501] [EC:1.14.16.2]
            4129  MAOB; monoamine oxidase B [KO:K00274] [EC:1.4.3.4]
            4128  MAOA; monoamine oxidase A [KO:K00274] [EC:1.4.3.4]
            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]
            4891  SLC11A2; solute carrier family 11 member 2 [KO:K21398]
            29986  SLC39A2; solute carrier family 39 member 2 [KO:K14709]
            29985  SLC39A3; solute carrier family 39 member 3 [KO:K14709]
            27173  SLC39A1; solute carrier family 39 member 1 [KO:K14709]
            55630  SLC39A4; solute carrier family 39 member 4 [KO:K14710]
            283375  SLC39A5; solute carrier family 39 member 5 [KO:K14711]
            25800  SLC39A6; solute carrier family 39 member 6 [KO:K14712]
            7922  SLC39A7; solute carrier family 39 member 7 [KO:K14713]
            64116  SLC39A8; solute carrier family 39 member 8 [KO:K14714]
            55334  SLC39A9; solute carrier family 39 member 9 [KO:K14715]
            57181  SLC39A10; solute carrier family 39 member 10 [KO:K14716]
            201266  SLC39A11; solute carrier family 39 member 11 [KO:K14717]
            221074  SLC39A12; solute carrier family 39 member 12 [KO:K14718]
            91252  SLC39A13; solute carrier family 39 member 13 [KO:K14719]
            23516  SLC39A14; solute carrier family 39 member 14 [KO:K14720]
            4535  ND1; NADH dehydrogenase subunit 1 [KO:K03878] [EC:7.1.1.2]
            4536  ND2; NADH dehydrogenase subunit 2 [KO:K03879] [EC:7.1.1.2]
            4537  ND3; NADH dehydrogenase subunit 3 [KO:K03880] [EC:7.1.1.2]
            4538  ND4; NADH dehydrogenase subunit 4 [KO:K03881] [EC:7.1.1.2]
            4539  ND4L; NADH dehydrogenase subunit 4L [KO:K03882] [EC:7.1.1.2]
            4540  ND5; NADH dehydrogenase subunit 5 [KO:K03883] [EC:7.1.1.2]
            4541  ND6; NADH dehydrogenase subunit 6 [KO:K03884] [EC:7.1.1.2]
            4723  NDUFV1; NADH:ubiquinone oxidoreductase core subunit V1 [KO:K03942] [EC:7.1.1.2]
            4729  NDUFV2; NADH:ubiquinone oxidoreductase core subunit V2 [KO:K03943] [EC:7.1.1.2]
            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; NDUFA4 mitochondrial complex associated 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:7.1.1.2]
            4720  NDUFS2; NADH:ubiquinone oxidoreductase core subunit S2 [KO:K03935] [EC:7.1.1.2]
            4722  NDUFS3; NADH:ubiquinone oxidoreductase core subunit S3 [KO:K03936] [EC:7.1.1.2]
            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:7.1.1.2]
            4728  NDUFS8; NADH:ubiquinone oxidoreductase core subunit S8 [KO:K03941] [EC:7.1.1.2]
            4717  NDUFC1; NADH:ubiquinone oxidoreductase subunit C1 [KO:K03967]
            4718  NDUFC2; NADH:ubiquinone oxidoreductase subunit C2 [KO:K03968]
            100532726  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:7.1.1.8]
            4519  CYTB; cytochrome b [KO:K00412]
            1537  CYC1; cytochrome c1 [KO:K00413]
            7384  UQCRC1; ubiquinol-cytochrome c reductase core protein 1 [KO:K00414]
            7385  UQCRC2; ubiquinol-cytochrome c reductase core protein 2 [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 subunit III [KO:K02262]
            4512  COX1; cytochrome c oxidase subunit I [KO:K02256] [EC:7.1.1.9]
            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  ATP5F1A; ATP synthase F1 subunit alpha [KO:K02132]
            506  ATP5F1B; ATP synthase F1 subunit beta [KO:K02133] [EC:7.1.2.2]
            509  ATP5F1C; ATP synthase F1 subunit gamma [KO:K02136]
            513  ATP5F1D; ATP synthase F1 subunit delta [KO:K02134]
            514  ATP5F1E; ATP synthase F1 subunit epsilon [KO:K02135]
            4508  ATP6; ATP synthase F0 subunit 6 [KO:K02126]
            515  ATP5PB; ATP synthase peripheral stalk-membrane subunit b [KO:K02127]
            516  ATP5MC1; ATP synthase membrane subunit c locus 1 [KO:K02128]
            517  ATP5MC2; ATP synthase membrane subunit c locus 2 [KO:K02128]
            518  ATP5MC3; ATP synthase membrane subunit c locus 3 [KO:K02128]
            10476  ATP5PD; ATP synthase peripheral stalk subunit d [KO:K02138]
            539  ATP5PO; ATP synthase peripheral stalk subunit OSCP [KO:K02137]
            522  ATP5PF; ATP synthase peripheral stalk subunit F6 [KO:K02131]
            4509  ATP8; ATP synthase F0 subunit 8 [KO:K02125]
            65018  PINK1; PTEN induced kinase 1 [KO:K05688] [EC:2.7.11.1]
            90550  MCU; mitochondrial calcium uniporter [KO:K20858]
            120892  LRRK2; leucine rich repeat kinase 2 [KO:K08844] [EC:2.7.11.1]
            27429  HTRA2; HtrA serine peptidase 2 [KO:K08669] [EC:3.4.21.108]
            10131  TRAP1; TNF receptor associated protein 1 [KO:K09488]
            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]
            11315  PARK7; Parkinsonism associated deglycase [KO:K05687] [EC:3.5.1.124]
            598  BCL2L1; BCL2 like 1 [KO:K04570]
            581  BAX; BCL2 associated X, apoptosis regulator [KO:K02159]
            55669  MFN1; mitofusin 1 [KO:K21356] [EC:3.6.5.-]
            9927  MFN2; mitofusin 2 [KO:K06030] [EC:3.6.5.-]
            3798  KIF5A; kinesin family member 5A [KO:K10396]
            3799  KIF5B; kinesin family member 5B [KO:K10396]
            3800  KIF5C; kinesin family member 5C [KO:K10396]
            147700  KLC3; kinesin light chain 3 [KO:K10407]
            3831  KLC1; kinesin light chain 1 [KO:K10407]
            64837  KLC2; kinesin light chain 2 [KO:K10407]
            89953  KLC4; kinesin light chain 4 [KO:K10407]
            10376  TUBA1B; tubulin alpha 1b [KO:K07374]
            7277  TUBA4A; tubulin alpha 4a [KO:K07374]
            7278  TUBA3C; tubulin alpha 3c [KO:K07374]
            7846  TUBA1A; tubulin alpha 1a [KO:K07374]
            84790  TUBA1C; tubulin alpha 1c [KO:K07374]
            51807  TUBA8; tubulin alpha 8 [KO:K07374]
            112714  TUBA3E; tubulin alpha 3e [KO:K07374]
            113457  TUBA3D; tubulin alpha 3d [KO:K07374]
            79861  TUBAL3; tubulin alpha like 3 [KO:K07374]
            84617  TUBB6; tubulin beta 6 class V [KO:K07375]
            203068  TUBB; tubulin beta class I [KO:K07375]
            81027  TUBB1; tubulin beta 1 class VI [KO:K07375]
            7280  TUBB2A; tubulin beta 2A class IIa [KO:K07375]
            10381  TUBB3; tubulin beta 3 class III [KO:K07375]
            10382  TUBB4A; tubulin beta 4A class IVa [KO:K07375]
            347688  TUBB8; tubulin beta 8 class VIII [KO:K07375]
            347733  TUBB2B; tubulin beta 2B class IIb [KO:K07375]
            10383  TUBB4B; tubulin beta 4B class IVb [KO:K07375]
            7157  TP53; tumor protein p53 [KO:K04451]
            1843  DUSP1; dual specificity phosphatase 1 [KO:K21278] [EC:3.1.3.16 3.1.3.48]
            4780  NFE2L2; NFE2 like bZIP transcription factor 2 [KO:K05638]
            7295  TXN; thioredoxin [KO:K03671]
            25828  TXN2; thioredoxin 2 [KO:K03671]
            1616  DAXX; death domain associated protein [KO:K02308]
            4217  MAP3K5; mitogen-activated protein kinase kinase kinase 5 [KO:K04426] [EC:2.7.11.25]
            5599  MAPK8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
            5602  MAPK10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
            5601  MAPK9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
            6647  SOD1; superoxide dismutase 1 [KO:K04565] [EC:1.15.1.1]
            9817  KEAP1; kelch like ECH associated protein 1 [KO:K10456]
COMPOUND    C00002  ATP
            C00007  Oxygen
            C00008  ADP
            C00009  Orthophosphate
            C00013  Diphosphate
            C00020  AMP
            C00027  Hydrogen peroxide
            C00034  Manganese
            C00076  Calcium cation
            C00082  L-Tyrosine
            C00165  Diacylglycerol
            C00212  Adenosine
            C00355  3,4-Dihydroxy-L-phenylalanine
            C00575  3',5'-Cyclic AMP
            C00704  Superoxide
            C01245  D-myo-Inositol 1,4,5-trisphosphate
            C03758  Dopamine
            C04043  3,4-Dihydroxyphenylacetaldehyde
            C04599  1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
            C07593  Rotenone
            C11310  1-Methyl-4-phenylpyridinium
            C14701  Paraquat
            C15231  Maneb
            C16844  Hydroxyl radical
            C17755  Dopamine quinone
            C22381  Reactive oxygen species
REFERENCE   PMID:16495942
  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)
            DOI:10.1038/nrn1868
REFERENCE   PMID:12938733
  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)
            DOI:10.1080/1521654031000153030
REFERENCE   PMID:26501339
  AUTHORS   Bobela W, Aebischer P, Schneider BL
  TITLE     Alphalpha-Synuclein as a Mediator in the Interplay between Aging and Parkinson's Disease.
  JOURNAL   Biomolecules 5:2675-700 (2015)
            DOI:10.3390/biom5042675
REFERENCE   PMID:15767499
  AUTHORS   Eriksen JL, Wszolek Z, Petrucelli L
  TITLE     Molecular pathogenesis of Parkinson disease.
  JOURNAL   Arch Neurol 62:353-7 (2005)
            DOI:10.1001/archneur.62.3.353
REFERENCE   PMID:16972273
  AUTHORS   Olanow CW, McNaught KS
  TITLE     Ubiquitin-proteasome system and Parkinson's disease.
  JOURNAL   Mov Disord 21:1806-23 (2006)
            DOI:10.1002/mds.21013
REFERENCE   PMID:18047737
  AUTHORS   Lim KL, Tan JM
  TITLE     Role of the ubiquitin proteasome system in Parkinson's disease.
  JOURNAL   BMC Biochem 8 Suppl 1:S13 (2007)
            DOI:10.1186/1471-2091-8-S1-S13
REFERENCE   PMID:29090092
  AUTHORS   Maiti P, Manna J, Dunbar GL
  TITLE     Current understanding of the molecular mechanisms in Parkinson's disease: Targets for potential treatments.
  JOURNAL   Transl Neurodegener 6:28 (2017)
            DOI:10.1186/s40035-017-0099-z
REFERENCE   PMID:12814656
  AUTHORS   Dev KK, van der Putten H, Sommer B, Rovelli G
  TITLE     Part I: parkin-associated proteins and Parkinson's disease.
  JOURNAL   Neuropharmacology 45:1-13 (2003)
            DOI:10.1016/s0028-3908(02)00337-4
REFERENCE   PMID:20495568
  AUTHORS   Obeso JA, Rodriguez-Oroz MC, Goetz CG, Marin C, Kordower JH, Rodriguez M, Hirsch EC, Farrer M, Schapira AH, Halliday G
  TITLE     Missing pieces in the Parkinson's disease puzzle.
  JOURNAL   Nat Med 16:653-61 (2010)
            DOI:10.1038/nm.2165
REFERENCE   PMID:24781149
  AUTHORS   Cali T, Ottolini D, Brini M
  TITLE     Calcium signaling in Parkinson's disease.
  JOURNAL   Cell Tissue Res 357:439-54 (2014)
            DOI:10.1007/s00441-014-1866-0
REFERENCE   PMID:19230774
  AUTHORS   Bezprozvanny I
  TITLE     Calcium signaling and neurodegenerative diseases.
  JOURNAL   Trends Mol Med 15:89-100 (2009)
            DOI:10.1016/j.molmed.2009.01.001
REFERENCE   PMID:28468938
  AUTHORS   Zaichick SV, McGrath KM, Caraveo G
  TITLE     The role of Ca(2+) signaling in Parkinson's disease.
  JOURNAL   Dis Model Mech 10:519-535 (2017)
            DOI:10.1242/dmm.028738
REFERENCE   PMID:28838811
  AUTHORS   Ludtmann MHR, Abramov AY
  TITLE     Mitochondrial calcium imbalance in Parkinson's disease.
  JOURNAL   Neurosci Lett 663:86-90 (2018)
            DOI:10.1016/j.neulet.2017.08.044
REFERENCE   PMID:19663908
  AUTHORS   Sandebring A, Dehvari N, Perez-Manso M, Thomas KJ, Karpilovski E, Cookson MR, Cowburn RF, Cedazo-Minguez A
  TITLE     Parkin deficiency disrupts calcium homeostasis by modulating phospholipase C signalling.
  JOURNAL   FEBS J 276:5041-52 (2009)
            DOI:10.1111/j.1742-4658.2009.07201.x
REFERENCE   PMID:23352769
  AUTHORS   Mercado G, Valdes P, Hetz C
  TITLE     An ERcentric view of Parkinson's disease.
  JOURNAL   Trends Mol Med 19:165-75 (2013)
            DOI:10.1016/j.molmed.2012.12.005
REFERENCE   PMID:27103567
  AUTHORS   Mercado G, Castillo V, Soto P, Sidhu A
  TITLE     ER stress and Parkinson's disease: Pathological inputs that converge into the secretory pathway.
  JOURNAL   Brain Res 1648:626-632 (2016)
            DOI:10.1016/j.brainres.2016.04.042
REFERENCE   PMID:26297973
  AUTHORS   Tsujii S, Ishisaka M, Hara H
  TITLE     Modulation of endoplasmic reticulum stress in Parkinson's disease.
  JOURNAL   Eur J Pharmacol 765:154-6 (2015)
            DOI:10.1016/j.ejphar.2015.08.033
REFERENCE   PMID:31100053
  AUTHORS   Shah A, Chao J, Legido-Quigley C, Chang RC
  TITLE     Oxyresveratrol exerts ATF4- and Grp78-mediated neuroprotection against endoplasmic reticulum stress in experimental Parkinson's disease.
  JOURNAL   Nutr Neurosci 1-16 (2019)
            DOI:10.1080/1028415X.2019.1613764
REFERENCE   PMID:24548101
  AUTHORS   Segura-Aguilar J, Paris I, Munoz P, Ferrari E, Zecca L, Zucca FA
  TITLE     Protective and toxic roles of dopamine in Parkinson's disease.
  JOURNAL   J Neurochem 129:898-915 (2014)
            DOI:10.1111/jnc.12686
REFERENCE   PMID:31587020
  AUTHORS   Jesko H, Lenkiewicz AM, Wilkaniec A, Adamczyk A
  TITLE     The interplay between parkin and alpha-synuclein; possible implications for the pathogenesis of Parkinson's disease.
  JOURNAL   Acta Neurobiol Exp (Wars) 79:276-289 (2019)
REFERENCE   PMID:15189334
  AUTHORS   Perez RG, Hastings TG
  TITLE     Could a loss of alpha-synuclein function put dopaminergic neurons at risk?
  JOURNAL   J Neurochem 89:1318-24 (2004)
            DOI:10.1111/j.1471-4159.2004.02423.x
REFERENCE   PMID:26487845
  AUTHORS   Segura-Aguilar J
  TITLE     A new mechanism for protection of dopaminergic neurons mediated by astrocytes.
  JOURNAL   Neural Regen Res 10:1225-7 (2015)
            DOI:10.4103/1673-5374.162750
REFERENCE   PMID:27546335
  AUTHORS   Bose A, Beal MF
  TITLE     Mitochondrial dysfunction in Parkinson's disease.
  JOURNAL   J Neurochem 139 Suppl 1:216-231 (2016)
            DOI:10.1111/jnc.13731
REFERENCE   PMID:27581196
  AUTHORS   Cieri D, Brini M, Cali T
  TITLE     Emerging (and converging) pathways in Parkinson's disease: keeping mitochondrial wellness.
  JOURNAL   Biochem Biophys Res Commun 483:1020-1030 (2017)
            DOI:10.1016/j.bbrc.2016.08.153
REFERENCE   PMID:27829983
  AUTHORS   Mack JM, Schamne MG, Sampaio TB, Pertile RA, Fernandes PA, Markus RP, Prediger RD
  TITLE     Melatoninergic System in Parkinson's Disease: From Neuroprotection to the Management of Motor and Nonmotor Symptoms.
  JOURNAL   Oxid Med Cell Longev 2016:3472032 (2016)
            DOI:10.1155/2016/3472032
REFERENCE   PMID:21674642
  AUTHORS   Cali T, Ottolini D, Brini M
  TITLE     Mitochondria, calcium, and endoplasmic reticulum stress in Parkinson's disease.
  JOURNAL   Biofactors 37:228-40 (2011)
            DOI:10.1002/biof.159
REFERENCE   PMID:24522549
  AUTHORS   Gaki GS, Papavassiliou AG
  TITLE     Oxidative stress-induced signaling pathways implicated in the pathogenesis of Parkinson's disease.
  JOURNAL   Neuromolecular Med 16:217-30 (2014)
            DOI:10.1007/s12017-014-8294-x
REFERENCE   PMID:25761946
  AUTHORS   Franco-Iborra S, Vila M, Perier C
  TITLE     The Parkinson Disease Mitochondrial Hypothesis: Where Are We at?
  JOURNAL   Neuroscientist 22:266-77 (2016)
            DOI:10.1177/1073858415574600
REFERENCE   PMID:22926193
  AUTHORS   de Vries RL, Przedborski S
  TITLE     Mitophagy and Parkinson's disease: be eaten to stay healthy.
  JOURNAL   Mol Cell Neurosci 55:37-43 (2013)
            DOI:10.1016/j.mcn.2012.07.008
REFERENCE   PMID:20736035
  AUTHORS   Deas E, Wood NW, Plun-Favreau H
  TITLE     Mitophagy and Parkinson's disease: the PINK1-parkin link.
  JOURNAL   Biochim Biophys Acta 1813:623-33 (2011)
            DOI:10.1016/j.bbamcr.2010.08.007
REFERENCE   PMID:25611507
  AUTHORS   Pickrell AM, Youle RJ
  TITLE     The roles of PINK1, parkin, and mitochondrial fidelity in Parkinson's disease.
  JOURNAL   Neuron 85:257-73 (2015)
            DOI:10.1016/j.neuron.2014.12.007
REFERENCE   PMID:27911343
  AUTHORS   Truban D, Hou X, Caulfield TR, Fiesel FC, Springer W
  TITLE     PINK1, Parkin, and Mitochondrial Quality Control: What can we Learn about Parkinson's Disease Pathobiology?
  JOURNAL   J Parkinsons Dis 7:13-29 (2017)
            DOI:10.3233/JPD-160989
REFERENCE   PMID:28823929
  AUTHORS   Biosa A, Sandrelli F, Beltramini M, Greggio E, Bubacco L, Bisaglia M
  TITLE     Recent findings on the physiological function of DJ-1: Beyond Parkinson's disease.
  JOURNAL   Neurobiol Dis 108:65-72 (2017)
            DOI:10.1016/j.nbd.2017.08.005
REFERENCE   PMID:29147906
  AUTHORS   Oh SE, Mouradian MM
  TITLE     Regulation of Signal Transduction by DJ-1.
  JOURNAL   Adv Exp Med Biol 1037:97-131 (2017)
            DOI:10.1007/978-981-10-6583-5_8
REFERENCE   PMID:31054074
  AUTHORS   Dolgacheva LP, Berezhnov AV, Fedotova EI, Zinchenko VP, Abramov AY
  TITLE     Role of DJ-1 in the mechanism of pathogenesis of Parkinson's disease.
  JOURNAL   J Bioenerg Biomembr 51:175-188 (2019)
            DOI:10.1007/s10863-019-09798-4
REFERENCE   PMID:30370500
  AUTHORS   Melo TQ, Copray SJCVM, Ferrari MFR
  TITLE     Alpha-Synuclein Toxicity on Protein Quality Control, Mitochondria and Endoplasmic Reticulum.
  JOURNAL   Neurochem Res 43:2212-2223 (2018)
            DOI:10.1007/s11064-018-2673-x
REFERENCE   PMID:30937538
  AUTHORS   Zhai S, Shen W, Graves SM, Surmeier DJ
  TITLE     Dopaminergic modulation of striatal function and Parkinson's disease.
  JOURNAL   J Neural Transm (Vienna) 126:411-422 (2019)
            DOI:10.1007/s00702-019-01997-y
REFERENCE   PMID:29720658
  AUTHORS   Parker JG, Marshall JD, Ahanonu B, Wu YW, Kim TH, Grewe BF, Zhang Y, Li JZ, Ding JB, Ehlers MD, Schnitzer MJ
  TITLE     Diametric neural ensemble dynamics in parkinsonian and dyskinetic states.
  JOURNAL   Nature 557:177-182 (2018)
            DOI:10.1038/s41586-018-0090-6
REL_PATHWAY hsa00190  Oxidative phosphorylation
            hsa00350  Tyrosine metabolism
            hsa03050  Proteasome
            hsa04020  Calcium signaling pathway
            hsa04120  Ubiquitin mediated proteolysis
            hsa04137  Mitophagy - animal
            hsa04141  Protein processing in endoplasmic reticulum
            hsa04210  Apoptosis
            hsa04728  Dopaminergic synapse
KO_PATHWAY  ko05012
///
