KEGG   DISEASE: Parkinson disease
H00057                      Disease                                
Parkinson disease
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.
Neurodegenerative disease
Human diseases in ICD-11 classification [BR:br08403]
 08 Diseases of the nervous system
  Movement disorders
   8A00  Parkinsonism
    H00057  Parkinson disease
Pathway-based classification of diseases [BR:br08402]
 Amino acid metabolism
  nt06028  Dopamine and serotonin metabolism
   H00057  Parkinson disease
 Cellular process
  nt06534  Unfolded protein response
   H00057  Parkinson disease
  nt06536  Mitophagy
   H00057  Parkinson disease
  nt06535  Efferocytosis
   H00057  Parkinson disease
hsa05012  Parkinson disease
hsa04137  Mitophagy - animal
nt06028 Dopamine and serotonin metabolism
nt06463 Parkinson disease
nt06466 Pathways of neurodegeneration
nt06534 Unfolded protein response
nt06535 Efferocytosis
nt06536 Mitophagy
(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]
(PARK25) PTPA [HSA:5524] [KO:K17605]
(IDLDP) NR4A2 [HSA:4929] [KO:K08558]
MAPT [HSA:4137] [KO:K04380]
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]
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 620482 619911 260540
Hardy J, Lewis P, Revesz T, Lees A, Paisan-Ruiz C
The genetics of Parkinson's syndromes: a critical review.
Curr Opin Genet Dev 19:254-65 (2009)
PMID:17582365 (PARK2, PARK6, PARK8)
Klein C, Lohmann-Hedrich K, Rogaeva E, Schlossmacher MG, Lang AE
Deciphering the role of heterozygous mutations in genes associated with parkinsonism.
Lancet Neurol 6:652-62 (2007)
PMID:17499497 (PARK2, PARK6, PARK7)
Dodson MW, Guo M
Pink1, Parkin, DJ-1 and mitochondrial dysfunction in Parkinson's disease.
Curr Opin Neurobiol 17:331-7 (2007)
PMID:12953260 (PARK7)
Abou-Sleiman PM, Healy DG, Quinn N, Lees AJ, Wood NW
The role of pathogenic DJ-1 mutations in Parkinson's disease.
Ann Neurol 54:283-6 (2003)
PMID:19182805 (PARK9)
Gitler AD, Chesi A, Geddie ML, Strathearn KE, Hamamichi S, Hill KJ, Caldwell KA, Caldwell GA, Cooper AA, Rochet JC, Lindquist S
Alpha-synuclein is part of a diverse and highly conserved interaction network that includes PARK9 and manganese toxicity.
Nat Genet 41:308-15 (2009)
PMID:19297401 (PARK1-15)
Lesage S, Brice A
Parkinson's disease: from monogenic forms to genetic susceptibility factors.
Hum Mol Genet 18:R48-59 (2009)
PMID:27090875 (PARK17, PARK18, PARK19)
Hernandez DG, Reed X, Singleton AB
Genetics in Parkinson disease: Mendelian versus non-Mendelian inheritance.
J Neurochem 139 Suppl 1:59-74 (2016)
PMID:25662902 (PARK22)
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
CHCHD2 mutations in autosomal dominant late-onset Parkinson's disease: a genome-wide linkage and sequencing study.
Lancet Neurol 14:274-82 (2015)
PMID:26942284 (PARK23)
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
Loss of VPS13C Function in Autosomal-Recessive Parkinsonism Causes Mitochondrial Dysfunction and Increases PINK1/Parkin-Dependent Mitophagy.
Am J Hum Genet 98:500-13 (2016)
PMID:32201884 (PARK24)
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
Variants in saposin D domain of prosaposin gene linked to Parkinson's disease.
Brain 143:1190-1205 (2020)
PMID:36073231 (PARK25)
Fevga C, Tesson C, Carreras Mascaro A, Courtin T, van Coller R, Sakka S, Ferraro F, Farhat N, Bardien S, Damak M, Carr J, Ferrien M, Boumeester V, Hundscheid J, Grillenzoni N, Kessissoglou IA, Kuipers DJS, Quadri M, Corvol JC, Mhiri C, Hassan BA, Breedveld GJ, Lesage S, Mandemakers W, Brice A, Bonifati V
PTPA variants and impaired PP2A activity in early-onset parkinsonism with intellectual disability.
Brain 146:1496-1510 (2023)
PMID:31428396 (IDLDP)
Ramos LLP, Monteiro FP, Sampaio LPB, Costa LA, Ribeiro MDO, Freitas EL, Kitajima JP, Kok F
Heterozygous loss of function of NR4A2 is associated with intellectual deficiency, rolandic epilepsy, and language impairment.
Clin Case Rep 7:1582-1584 (2019)
PMID:11220749 (MAPT)
Pastor P, Pastor E, Carnero C, Vela R, Garcia T, Amer G, Tolosa E, Oliva R
Familial atypical progressive supranuclear palsy associated with homozigosity for the delN296 mutation in the tau gene.

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