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KEGG   PATHWAY: hsa05143
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
hsa05143

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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
Related
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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