KEGG   DISEASE: Parkinson disease
Entry
H00057                      Disease                                
Name
Parkinson disease
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.
Category
Neurodegenerative disease
Brite
Human diseases [BR:br08402]
 Nervous system diseases
  Neurodegenerative diseases
   H00057  Parkinson disease
Human diseases in ICD-11 classification [BR:br08403]
 08 Diseases of the nervous system
  Movement disorders
   8A00  Parkinsonism
    H00057  Parkinson disease
Pathway
hsa05012  Parkinson disease
Related
pathway
hsa05022  Pathways of neurodegeneration - multiple diseases
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
nt06463  Parkinson disease
Gene
(PARK1/PARK4) SNCA (duplication, triplication) [HSA:6622] [KO:K04528]
(PARK2) PRKN [HSA:5071] [KO:K04556]
(PARK5) UCHL1 [HSA:7345] [KO:K05611]
(PARK6) PINK1 [HSA:65018] [KO:K05688]
(PARK7) PARK7 [HSA:11315] [KO:K05687]
(PARK8) LRRK2 [HSA:120892] [KO:K08844]
(PARK9) ATP13A2 [HSA:23400] [KO:K13526]
(PARK11) GIGYF2 [HSA:26058] [KO:K18730]
(PARK13) HTRA2 [HSA:27429] [KO:K08669]
(PARK14) PLA2G6 [HSA:8398] [KO:K16343]
(PARK15) FBXO7 [HSA:25793] [KO:K10293]
(PARK17) VPS35 [HSA:55737] [KO:K18468]
(PARK18) EIF4G1 [HSA:1981] [KO:K03260]
(PARK19) DNAJC6 [HSA:9829] [KO:K09526]
(PARK22) CHCHD2 [HSA:51142] [KO:K22758]
(PARK23) VPS13C [HSA:54832] [KO:K19525]
(PARK24) PSAP [HSA:5660] [KO:K12382]
NR4A2 [HSA:4929] [KO:K08558]
MAPT [HSA:4137] [KO:K04380]
Env factor
MPTP [CPD:C04599]
Rotenone [CPD:C07593]
Maneb [CPD:C15231]
Paraquat [CPD:C14701]
Drug
Droxidopa [DR:D01277]
Bromocriptine mesylate [DR:D00780]
Apomorphine hydrochloride [DR:D02004]
Levodopa [DR:D00059]
Carbidopa hydrate and levodopa [DR:D00253]
Carbidopa, levodopa and entacapone [DR:D10293]
Amantadine hydrochloride [DR:D00777]
Ropinirole hydrochloride [DR:D00784]
Pramipexole dihydrochloride [DR:D00559]
Rotigotine [DR:D05768]
Selegiline hydrochloride [DR:D00785]
Rasagiline mesylate [DR:D02562]
Safinamide mesylate [DR:D10191]
Tolcapone [DR:D00786]
Entacapone [DR:D00781]
Opicapone [DR:D10825]
Istradefylline [DR:D04641]
Pimavanserin tartrate [DR:D08969]
Carbidopa [DR:D00558]
Comment
Disease class: synucleinopathy
Affected region: substantia nigra, putamen, caudate nucleus, hypothalamus
Microscopic lesion: Lewy bodies
Other DBs
ICD-11: 8A00.0
ICD-10: G20
MeSH: D010300
OMIM: 168600 168601 605543 600116 605909 606324 607060 606693 607688 610297 612953 260300 614203 614251 615528 616710 616840 619491
Reference
  Authors
Hardy J, Lewis P, Revesz T, Lees A, Paisan-Ruiz C
  Title
The genetics of Parkinson's syndromes: a critical review.
  Journal
Curr Opin Genet Dev 19:254-65 (2009)
DOI:10.1016/j.gde.2009.03.008
Reference
PMID:17582365 (PARK2, PARK6, PARK8)
  Authors
Klein C, Lohmann-Hedrich K, Rogaeva E, Schlossmacher MG, Lang AE
  Title
Deciphering the role of heterozygous mutations in genes associated with parkinsonism.
  Journal
Lancet Neurol 6:652-62 (2007)
DOI:10.1016/S1474-4422(07)70174-6
Reference
PMID:17499497 (PARK2, PARK6, PARK7)
  Authors
Dodson MW, Guo M
  Title
Pink1, Parkin, DJ-1 and mitochondrial dysfunction in Parkinson's disease.
  Journal
Curr Opin Neurobiol 17:331-7 (2007)
DOI:10.1016/j.conb.2007.04.010
Reference
PMID:12953260 (PARK7)
  Authors
Abou-Sleiman PM, Healy DG, Quinn N, Lees AJ, Wood NW
  Title
The role of pathogenic DJ-1 mutations in Parkinson's disease.
  Journal
Ann Neurol 54:283-6 (2003)
DOI:10.1002/ana.10675
Reference
PMID:19182805 (PARK9)
  Authors
Gitler AD, Chesi A, Geddie ML, Strathearn KE, Hamamichi S, Hill KJ, Caldwell KA, Caldwell GA, Cooper AA, Rochet JC, Lindquist S
  Title
Alpha-synuclein is part of a diverse and highly conserved interaction network that includes PARK9 and manganese toxicity.
  Journal
Nat Genet 41:308-15 (2009)
DOI:10.1038/ng.300
Reference
PMID:19297401 (PARK1-15)
  Authors
Lesage S, Brice A
  Title
Parkinson's disease: from monogenic forms to genetic susceptibility factors.
  Journal
Hum Mol Genet 18:R48-59 (2009)
DOI:10.1093/hmg/ddp012
Reference
PMID:27090875 (PARK17, PARK18, PARK19)
  Authors
Hernandez DG, Reed X, Singleton AB
  Title
Genetics in Parkinson disease: Mendelian versus non-Mendelian inheritance.
  Journal
J Neurochem 139 Suppl 1:59-74 (2016)
DOI:10.1111/jnc.13593
Reference
PMID:25662902 (PARK22)
  Authors
Funayama M, Ohe K, Amo T, Furuya N, Yamaguchi J, Saiki S, Li Y, Ogaki K, Ando M, Yoshino H, Tomiyama H, Nishioka K, Hasegawa K, Saiki H, Satake W, Mogushi K, Sasaki R, Kokubo Y, Kuzuhara S, Toda T, Mizuno Y, Uchiyama Y, Ohno K, Hattori N
  Title
CHCHD2 mutations in autosomal dominant late-onset Parkinson's disease: a genome-wide linkage and sequencing study.
  Journal
Lancet Neurol 14:274-82 (2015)
DOI:10.1016/S1474-4422(14)70266-2
Reference
PMID:26942284 (PARK23)
  Authors
Lesage S, Drouet V, Majounie E, Deramecourt V, Jacoupy M, Nicolas A, Cormier-Dequaire F, Hassoun SM, Pujol C, Ciura S, Erpapazoglou Z, Usenko T, Maurage CA, Sahbatou M, Liebau S, Ding J, Bilgic B, Emre M, Erginel-Unaltuna N, Guven G, Tison F, Tranchant C, Vidailhet M, Corvol JC, Krack P, Leutenegger AL, Nalls MA, Hernandez DG, Heutink P, Gibbs JR, Hardy J, Wood NW, Gasser T, Durr A, Deleuze JF, Tazir M, Destee A, Lohmann E, Kabashi E, Singleton A, Corti O, Brice A
  Title
Loss of VPS13C Function in Autosomal-Recessive Parkinsonism Causes Mitochondrial Dysfunction and Increases PINK1/Parkin-Dependent Mitophagy.
  Journal
Am J Hum Genet 98:500-13 (2016)
DOI:10.1016/j.ajhg.2016.01.014
Reference
PMID:32201884 (PARK24)
  Authors
Oji Y, Hatano T, Ueno SI, Funayama M, Ishikawa KI, Okuzumi A, Noda S, Sato S, Satake W, Toda T, Li Y, Hino-Takai T, Kakuta S, Tsunemi T, Yoshino H, Nishioka K, Hattori T, Mizutani Y, Mutoh T, Yokochi F, Ichinose Y, Koh K, Shindo K, Takiyama Y, Hamaguchi T, Yamada M, Farrer MJ, Uchiyama Y, Akamatsu W, Wu YR, Matsuda J, Hattori N
  Title
Variants in saposin D domain of prosaposin gene linked to Parkinson's disease.
  Journal
Brain 143:1190-1205 (2020)
DOI:10.1093/brain/awaa064
Reference
PMID:12496759 (NR4A2)
  Authors
Le WD, Xu P, Jankovic J, Jiang H, Appel SH, Smith RG, Vassilatis DK
  Title
Mutations in NR4A2 associated with familial Parkinson disease.
  Journal
Nat Genet 33:85-9 (2003)
DOI:10.1038/ng1066
Reference
PMID:11710889 (MAPT)
  Authors
Martin ER, Scott WK, Nance MA, Watts RL, Hubble JP, Koller WC, Lyons K, Pahwa R, Stern MB, Colcher A, Hiner BC, Jankovic J, Ondo WG, Allen FH Jr, Goetz CG, Small GW, Masterman D, Mastaglia F, Laing NG, Stajich JM, Ribble RC, Booze MW, Rogala A, Hauser MA, Zhang F, Gibson RA, Middleton LT, Roses AD, Haines JL, Scott BL, Pericak-Vance MA, Vance JM
  Title
Association of single-nucleotide polymorphisms of the tau gene with late-onset Parkinson disease.
  Journal
JAMA 286:2245-50 (2001)
DOI:10.1001/jama.286.18.2245

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