| H00057 | |
| H number | H00057 |
| 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 DIS_PATHWAY hsa05012 Parkinson disease |
| Network | 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] (IDLDP) NR4A2 [HSA:4929] [KO:K08558] MAPT [HSA:4137] [KO:K04380] |
| Pathogen | - |
| Env factor | - |
| Carcinogen | - |
| 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 619911 260540 |
| Reference | PMID:19419854 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 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 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 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 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 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 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 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 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 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 PMID:31428396 (IDLDP) AUTHORS Ramos LLP, Monteiro FP, Sampaio LPB, Costa LA, Ribeiro MDO, Freitas EL, Kitajima JP, Kok F TITLE Heterozygous loss of function of NR4A2 is associated with intellectual deficiency, rolandic epilepsy, and language impairment. JOURNAL Clin Case Rep 7:1582-1584 (2019) DOI:10.1002/ccr3.2260 PMID:11220749 (MAPT) AUTHORS Pastor P, Pastor E, Carnero C, Vela R, Garcia T, Amer G, Tolosa E, Oliva R TITLE Familial atypical progressive supranuclear palsy associated with homozigosity for the delN296 mutation in the tau gene. JOURNAL Ann Neurol 49:263-7 (2001) DOI:10.1002/1531-8249(20010201)49:2<263::aid-ana50>3.0.co;2-k |