KEGG   PATHWAY: hsa05020Help
Entry
hsa05020                    Pathway                                

Name
Prion diseases - Homo sapiens (human)
Description
Prion diseases, also termed transmissible spongiform encephalopathies (TSEs), are a group of fatal neurodegenerative diseases that affect humans and a number of other animal species. The etiology of these diseases is thought to be associated with the conversion of a normal protein, PrPC, into an infectious, pathogenic form, PrPSc. The conversion is induced by prion infections (for example, variant Creutzfeldt-Jakob disease (vCJD), iatrogenic CJD, Kuru), mutations (familial CJD, Gerstmann-Straussler-Scheinker syndrome, fatal familial insomnia (FFI)) or unknown factors (sporadic CJD (sCJD)), and is thought to occur after PrPC has reached the plasma membrane or is re-internalized for degradation. The PrPSc form shows greater protease resistance than PrPC and accumulates in affected individuals, often in the form of extracellular plaques. Pathways that may lead to neuronal death comprise oxidative stress, regulated activation of complement, ubiquitin-proteasome and endosomal-lysosomal systems, synaptic alterations and dendritic atrophy, corticosteroid response, and endoplasmic reticulum stress. In addition, the conformational transition could lead to the lost of a beneficial activity of the natively folded protein, PrPC.
Class
09160 Human Diseases; 09163 Neurodegenerative diseases
BRITE hierarchy
Pathway map
hsa05020  Prion diseases
hsa05020

Ortholog table
Disease
H00061  Prion diseases
Organism
Homo sapiens (human) [GN:hsa]
Gene
5621  PRNP; prion protein [KO:K05634]
3309  HSPA5; heat shock protein family A (Hsp70) member 5 [KO:K09490]
4684  NCAM1; neural cell adhesion molecule 1 [KO:K06491]
4685  NCAM2; neural cell adhesion molecule 2 [KO:K06491]
3915  LAMC1; laminin subunit gamma 1 [KO:K05635]
6647  SOD1; superoxide dismutase 1 [KO:K04565] [EC:1.15.1.1]
10963  STIP1; stress induced phosphoprotein 1 [KO:K09553]
5566  PRKACA; protein kinase cAMP-activated catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
5567  PRKACB; protein kinase cAMP-activated catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
5568  PRKACG; protein kinase cAMP-activated catalytic subunit gamma [KO:K04345] [EC:2.7.11.11]
581  BAX; BCL2 associated X, apoptosis regulator [KO:K02159]
2534  FYN; FYN proto-oncogene, Src family tyrosine kinase [KO:K05703] [EC:2.7.10.2]
100506742  CASP12; caspase 12 (gene/pseudogene) [KO:K04741] [EC:3.4.22.-]
727  C5; complement C5 [KO:K03994]
729  C6; complement C6 [KO:K03995]
730  C7; complement C7 [KO:K03996]
731  C8A; complement C8 alpha chain [KO:K03997]
732  C8B; complement C8 beta chain [KO:K03998]
733  C8G; complement C8 gamma chain [KO:K03999]
735  C9; complement C9 [KO:K04000]
712  C1QA; complement C1q A chain [KO:K03986]
713  C1QB; complement C1q B chain [KO:K03987]
714  C1QC; complement C1q C chain [KO:K03988]
4851  NOTCH1; notch 1 [KO:K02599]
5604  MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
5605  MAP2K2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
5594  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
5595  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
2002  ELK1; ELK1, ETS transcription factor [KO:K04375]
1958  EGR1; early growth response 1 [KO:K09203]
6352  CCL5; C-C motif chemokine ligand 5 [KO:K12499]
3552  IL1A; interleukin 1 alpha [KO:K04383]
3553  IL1B; interleukin 1 beta [KO:K04519]
3569  IL6; interleukin 6 [KO:K05405]
3303  HSPA1A; heat shock protein family A (Hsp70) member 1A [KO:K03283]
Compound
C00027  Hydrogen peroxide
C00575  3',5'-Cyclic AMP
C02140  Corticosterone
Reference
  Authors
Kovacs GG, Budka H
  Title
Prion diseases: from protein to cell pathology.
  Journal
Am J Pathol 172:555-65 (2008)
DOI:10.2353/ajpath.2008.070442
Reference
  Authors
Campana V, Sarnataro D, Zurzolo C
  Title
The highways and byways of prion protein trafficking.
  Journal
Trends Cell Biol 15:102-11 (2005)
DOI:10.1016/j.tcb.2004.12.002
Reference
  Authors
Nunziante M, Gilch S, Schatzl HM
  Title
Prion diseases: from molecular biology to intervention strategies.
  Journal
Chembiochem 4:1268-84 (2003)
DOI:10.1002/cbic.200300704
Reference
  Authors
Caughey B, Baron GS
  Title
Prions and their partners in crime.
  Journal
Nature 443:803-10 (2006)
DOI:10.1038/nature05294
Reference
  Authors
Linden R, Martins VR, Prado MA, Cammarota M, Izquierdo I, Brentani RR
  Title
Physiology of the prion protein.
  Journal
Physiol Rev 88:673-728 (2008)
DOI:10.1152/physrev.00007.2007
Reference
  Authors
Chiesa R, Harris DA
  Title
Prion diseases: what is the neurotoxic molecule?
  Journal
Neurobiol Dis 8:743-63 (2001)
DOI:10.1006/nbdi.2001.0433
Reference
  Authors
Harris DA
  Title
Cellular biology of prion diseases.
  Journal
Clin Microbiol Rev 12:429-44 (1999)
Reference
  Authors
Marella M, Gaggioli C, Batoz M, Deckert M, Tartare-Deckert S, Chabry J
  Title
Pathological prion protein exposure switches on neuronal mitogen-activated protein kinase pathway resulting in microglia recruitment.
  Journal
J Biol Chem 280:1529-34 (2005)
DOI:10.1074/jbc.M410966200
Reference
  Authors
Mallucci G, Collinge J
  Title
Rational targeting for prion therapeutics.
  Journal
Nat Rev Neurosci 6:23-34 (2005)
DOI:10.1038/nrn1584
Reference
  Authors
Hegde RS, Rane NS
  Title
Prion protein trafficking and the development of neurodegeneration.
  Journal
Trends Neurosci 26:337-9 (2003)
DOI:10.1016/S0166-2236(03)00143-7
Reference
  Authors
Fasano C, Campana V, Zurzolo C
  Title
Prions: protein only or something more? Overview of potential prion cofactors.
  Journal
J Mol Neurosci 29:195-214 (2006)
DOI:10.1385/JMN:29:3:195
Reference
  Authors
Roucou X, Gains M, LeBlanc AC
  Title
Neuroprotective functions of prion protein.
  Journal
J Neurosci Res 75:153-61 (2004)
DOI:10.1002/jnr.10864
Reference
  Authors
Novakofski J, Brewer MS, Mateus-Pinilla N, Killefer J, McCusker RH
  Title
Prion biology relevant to bovine spongiform encephalopathy.
  Journal
J Anim Sci 83:1455-76 (2005)
DOI:10.2527/2005.8361455x
Reference
  Authors
Aguzzi A, Baumann F, Bremer J
  Title
The prion's elusive reason for being.
  Journal
Annu Rev Neurosci 31:439-77 (2008)
DOI:10.1146/annurev.neuro.31.060407.125620
Reference
  Authors
Mabbott NA
  Title
The complement system in prion diseases.
  Journal
Curr Opin Immunol 16:587-93 (2004)
DOI:10.1016/j.coi.2004.07.002
KO pathway
ko05020   

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