| H00057 | |
| H番号 | H00057 |
| 名称 | パーキンソン病 |
| 概要 | 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. |
| カテゴリ | 神経変性疾患 疾患パスウェイ hsa05012 パーキンソン病 |
| ネットワーク | nt06410(H00057) Calcium signaling nt06412(H00057) Unfolded protein response (UPR) signaling nt06414(H00057) Apoptosis nt06418(H00057) Oxidative phosphorylation nt06419(H00057) Microtubule-based transport nt06420(H00057) Ubiquitin-proteasome system nt06421(H00057) Mitophagy nt06422(H00057) Dopamine metabolism nt06440(H00057) Transcription nt06463 Parkinson disease |
| 病因遺伝子 | (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] |
| 病原体 | - |
| 環境要因 | - |
| 発癌物質 | - |
| 治療薬 | ゾニサミド [DR:D00538] レボドパ [DR:D00059] ドロキシドパ [DR:D01277] カベルゴリン [DR:D00987] アポモルヒネ塩酸塩水和物 [DR:D02004] レボドパ・カルビドパ水和物 [DR:D00253] レボドパ・ベンセラジド塩酸塩 [DR:D02135] カルビドパ・レボドパ・エンタカポン [DR:D10293] ホスレボドパ・ホスカルビドパ水和物 [DR:D12494] ペルゴリドメシル酸塩 [DR:D00502] ロピニロール塩酸塩 [DR:D00784] プラミペキソール塩酸塩水和物 [DR:D00559] ロチゴチン [DR:D05768] セレギリン塩酸塩 [DR:D00785] ラサギリンメシル酸塩 [DR:D02562] サフィナミドメシル酸塩 [DR:D10191] エンタカポン [DR:D00781] オピカポン [DR:D10825] イストラデフィリン [DR:D04641] |
| コメント | Disease class: synucleinopathy Affected region: substantia nigra, putamen, caudate nucleus, hypothalamus Microscopic lesion: Lewy bodies |
| リンク | 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 |
| 文献 | PMID:19419854 著者 Hardy J, Lewis P, Revesz T, Lees A, Paisan-Ruiz C タイトル The genetics of Parkinson's syndromes: a critical review. 雑誌 Curr Opin Genet Dev 19:254-65 (2009) DOI:10.1016/j.gde.2009.03.008 PMID:17582365 (PARK2, PARK6, PARK8) 著者 Klein C, Lohmann-Hedrich K, Rogaeva E, Schlossmacher MG, Lang AE タイトル Deciphering the role of heterozygous mutations in genes associated with parkinsonism. 雑誌 Lancet Neurol 6:652-62 (2007) DOI:10.1016/S1474-4422(07)70174-6 PMID:17499497 (PARK2, PARK6, PARK7) 著者 Dodson MW, Guo M タイトル Pink1, Parkin, DJ-1 and mitochondrial dysfunction in Parkinson's disease. 雑誌 Curr Opin Neurobiol 17:331-7 (2007) DOI:10.1016/j.conb.2007.04.010 PMID:12953260 (PARK7) 著者 Abou-Sleiman PM, Healy DG, Quinn N, Lees AJ, Wood NW タイトル The role of pathogenic DJ-1 mutations in Parkinson's disease. 雑誌 Ann Neurol 54:283-6 (2003) DOI:10.1002/ana.10675 PMID:19182805 (PARK9) 著者 Gitler AD, Chesi A, Geddie ML, Strathearn KE, Hamamichi S, Hill KJ, Caldwell KA, Caldwell GA, Cooper AA, Rochet JC, Lindquist S タイトル Alpha-synuclein is part of a diverse and highly conserved interaction network that includes PARK9 and manganese toxicity. 雑誌 Nat Genet 41:308-15 (2009) DOI:10.1038/ng.300 PMID:19297401 (PARK1-15) 著者 Lesage S, Brice A タイトル Parkinson's disease: from monogenic forms to genetic susceptibility factors. 雑誌 Hum Mol Genet 18:R48-59 (2009) DOI:10.1093/hmg/ddp012 PMID:27090875 (PARK17, PARK18, PARK19) 著者 Hernandez DG, Reed X, Singleton AB タイトル Genetics in Parkinson disease: Mendelian versus non-Mendelian inheritance. 雑誌 J Neurochem 139 Suppl 1:59-74 (2016) DOI:10.1111/jnc.13593 PMID:25662902 (PARK22) 著者 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 タイトル CHCHD2 mutations in autosomal dominant late-onset Parkinson's disease: a genome-wide linkage and sequencing study. 雑誌 Lancet Neurol 14:274-82 (2015) DOI:10.1016/S1474-4422(14)70266-2 PMID:26942284 (PARK23) 著者 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 タイトル Loss of VPS13C Function in Autosomal-Recessive Parkinsonism Causes Mitochondrial Dysfunction and Increases PINK1/Parkin-Dependent Mitophagy. 雑誌 Am J Hum Genet 98:500-13 (2016) DOI:10.1016/j.ajhg.2016.01.014 PMID:32201884 (PARK24) 著者 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 タイトル Variants in saposin D domain of prosaposin gene linked to Parkinson's disease. 雑誌 Brain 143:1190-1205 (2020) DOI:10.1093/brain/awaa064 PMID:31428396 (IDLDP) 著者 Ramos LLP, Monteiro FP, Sampaio LPB, Costa LA, Ribeiro MDO, Freitas EL, Kitajima JP, Kok F タイトル Heterozygous loss of function of NR4A2 is associated with intellectual deficiency, rolandic epilepsy, and language impairment. 雑誌 Clin Case Rep 7:1582-1584 (2019) DOI:10.1002/ccr3.2260 PMID:11220749 (MAPT) 著者 Pastor P, Pastor E, Carnero C, Vela R, Garcia T, Amer G, Tolosa E, Oliva R タイトル Familial atypical progressive supranuclear palsy associated with homozigosity for the delN296 mutation in the tau gene. 雑誌 Ann Neurol 49:263-7 (2001) DOI:10.1002/1531-8249(20010201)49:2<263::aid-ana50>3.0.co;2-k |