ENTRY       hsa05143                    Pathway
NAME        African trypanosomiasis - Homo sapiens (human)
DESCRIPTION Trypanosoma brucei, the parasite responsible for African trypanosomiasis (sleeping sickness), are spread by the tsetse fly in sub-Saharan Africa. The parasites are able to pass through the blood-brain barrier and cause neurological damage by inducing cytokines like TNF alpha, IFN gamma, and IL1. These cytokines and other metabolites such as nitric oxide and somnogenic prostaglandin D2 disturb circadian rhythms in patients with African trypanosomiasis.
CLASS       Human Diseases; Infectious disease: parasitic
PATHWAY_MAP hsa05143  African trypanosomiasis
DISEASE     H00357  African trypanosomiasis
ORGANISM    Homo sapiens (human) [GN:hsa]
GENE        102723407  IGH; immunoglobulin heavy variable 4-38-2-like [KO:K06856]
            54106  TLR9; toll like receptor 9 [KO:K10161]
            4615  MYD88; MYD88 innate immune signal transduction adaptor [KO:K04729]
            7064  THOP1; thimet oligopeptidase 1 [KO:K01392] [EC:3.4.24.15]
            3827  KNG1; kininogen 1 [KO:K03898]
            4878  NPPA; natriuretic peptide A [KO:K12334]
            335  APOA1; apolipoprotein A1 [KO:K08757]
            8542  APOL1; apolipoprotein L1 [KO:K23585]
            3250  HPR; haptoglobin-related protein [KO:K14477]
            3039  HBA1; hemoglobin subunit alpha 1 [KO:K13822]
            3040  HBA2; hemoglobin subunit alpha 2 [KO:K13822]
            3043  HBB; hemoglobin subunit beta [KO:K13823]
            3586  IL10; interleukin 10 [KO:K05443]
            3592  IL12A; interleukin 12A [KO:K05406]
            3593  IL12B; interleukin 12B [KO:K05425]
            3606  IL18; interleukin 18 [KO:K05482]
            3458  IFNG; interferon gamma [KO:K04687]
            7124  TNF; tumor necrosis factor [KO:K03156]
            3553  IL1B; interleukin 1 beta [KO:K04519]
            3569  IL6; interleukin 6 [KO:K05405]
            356  FASLG; Fas ligand [KO:K04389]
            355  FAS; Fas cell surface death receptor [KO:K04390]
            7412  VCAM1; vascular cell adhesion molecule 1 [KO:K06527]
            6401  SELE; selectin E [KO:K06494]
            3383  ICAM1; intercellular adhesion molecule 1 [KO:K06490]
            3910  LAMA4; laminin subunit alpha 4 [KO:K06241]
            3620  IDO1; indoleamine 2,3-dioxygenase 1 [KO:K00463] [EC:1.13.11.52]
            169355  IDO2; indoleamine 2,3-dioxygenase 2 [KO:K00463] [EC:1.13.11.52]
            2150  F2RL1; F2R like trypsin receptor 1 [KO:K04234]
            2776  GNAQ; G protein subunit alpha q [KO:K04634]
            23236  PLCB1; phospholipase C beta 1 [KO:K05858] [EC:3.1.4.11]
            5330  PLCB2; phospholipase C beta 2 [KO:K05858] [EC:3.1.4.11]
            5331  PLCB3; phospholipase C beta 3 [KO:K05858] [EC:3.1.4.11]
            5332  PLCB4; phospholipase C beta 4 [KO:K05858] [EC:3.1.4.11]
            5578  PRKCA; protein kinase C alpha [KO:K02677] [EC:2.7.11.13]
            5579  PRKCB; protein kinase C beta [KO:K19662] [EC:2.7.11.13]
            5582  PRKCG; protein kinase C gamma [KO:K19663] [EC:2.7.11.13]
COMPOUND    C00076  Calcium cation
            C00078  L-Tryptophan
            C00165  Diacylglycerol
            C00328  L-Kynurenine
            C00533  Nitric oxide
            C00584  Prostaglandin E2
            C00696  Prostaglandin D2
            C01245  D-myo-Inositol 1,4,5-trisphosphate
REFERENCE   PMID:19168735
  AUTHORS   Antoine-Moussiaux N, Buscher P, Desmecht D
  TITLE     Host-parasite interactions in trypanosomiasis: on the way to an antidisease strategy.
  JOURNAL   Infect Immun 77:1276-84 (2009)
            DOI:10.1128/IAI.01185-08
REFERENCE   PMID:12088284
  AUTHORS   Enanga B, Burchmore RJ, Stewart ML, Barrett MP
  TITLE     Sleeping sickness and the brain.
  JOURNAL   Cell Mol Life Sci 59:845-58 (2002)
            DOI:10.1007/s00018-002-8472-0
REFERENCE   PMID:16600243
  AUTHORS   Bisser S, Ouwe-Missi-Oukem-Boyer ON, Toure FS, Taoufiq Z, Bouteille B, Buguet A, Mazier D
  TITLE     Harbouring in the brain: A focus on immune evasion mechanisms and their deleterious effects in malaria and human African trypanosomiasis.
  JOURNAL   Int J Parasitol 36:529-40 (2006)
            DOI:10.1016/j.ijpara.2006.02.001
REFERENCE   PMID:17582444
  AUTHORS   Masocha W, Rottenberg ME, Kristensson K
  TITLE     Migration of African trypanosomes across the blood-brain barrier.
  JOURNAL   Physiol Behav 92:110-4 (2007)
            DOI:10.1016/j.physbeh.2007.05.045
REFERENCE   PMID:11850009
  AUTHORS   Lonsdale-Eccles JD, Grab DJ
  TITLE     Trypanosome hydrolases and the blood-brain barrier.
  JOURNAL   Trends Parasitol 18:17-9 (2002)
            DOI:10.1016/S1471-4922(01)02120-1
REFERENCE   PMID:19016378
  AUTHORS   Grab DJ, Kennedy PG
  TITLE     Traversal of human and animal trypanosomes across the blood-brain barrier.
  JOURNAL   J Neurovirol 14:344-51 (2008)
            DOI:10.1080/13550280802282934
REFERENCE   PMID:19995590
  AUTHORS   Kristensson K, Nygard M, Bertini G, Bentivoglio M
  TITLE     African trypanosome infections of the nervous system: parasite entry and effects on sleep and synaptic functions.
  JOURNAL   Prog Neurobiol 91:152-71 (2010)
            DOI:10.1016/j.pneurobio.2009.12.001
REFERENCE   PMID:19559585
  AUTHORS   Pays E, Vanhollebeke B
  TITLE     Human innate immunity against African trypanosomes.
  JOURNAL   Curr Opin Immunol 21:493-8 (2009)
            DOI:10.1016/j.coi.2009.05.024
REFERENCE   PMID:9574925
  AUTHORS   Donelson JE, Hill KL, El-Sayed NM
  TITLE     Multiple mechanisms of immune evasion by African trypanosomes.
  JOURNAL   Mol Biochem Parasitol 91:51-66 (1998)
            DOI:10.1016/S0166-6851(97)00209-0
REFERENCE   PMID:19621073
  AUTHORS   Grab DJ, Garcia-Garcia JC, Nikolskaia OV, Kim YV, Brown A, Pardo CA, Zhang Y, Becker KG, Wilson BA, de A Lima AP, Scharfstein J, Dumler JS
  TITLE     Protease activated receptor signaling is required for African trypanosome traversal of human brain microvascular endothelial cells.
  JOURNAL   PLoS Negl Trop Dis 3:e479 (2009)
            DOI:10.1371/journal.pntd.0000479
REFERENCE   PMID:20398209
  AUTHORS   Vanhollebeke B, Pays E
  TITLE     The trypanolytic factor of human serum: many ways to enter the parasite, a single way to kill.
  JOURNAL   Mol Microbiol 76:806-14 (2010)
            DOI:10.1111/j.1365-2958.2010.07156.x
REL_PATHWAY hsa00380  Tryptophan metabolism
            hsa04210  Apoptosis
            hsa04610  Complement and coagulation cascades
            hsa04620  Toll-like receptor signaling pathway
            hsa04710  Circadian rhythm
KO_PATHWAY  ko05143
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