| Entry |
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| Name |
Prion diseases
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| 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.
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| Class |
Human Diseases; Neurodegenerative diseases
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| Pathway map |
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| Disease |
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| Orthology |
| prion protein | | heat shock 70kDa protein 5 | | neural cell adhesion molecule | | laminin, gamma 1 | | superoxide dismutase, Cu-Zn family [EC: 1.15.1.1] | | stress-induced-phosphoprotein 1 | | | | apoptosis regulator BAX | | tyrosine-protein kinase Fyn [EC: 2.7.10.2] | | caspase 12 [EC:3.4.22.-] | | complement component 5 | | complement component 6 | | complement component 7 | | complement component 8 subunit alpha | | complement component 8 subunit beta | | complement component 8 subunit gamma | | complement component 9 | | complement C1q subcomponent subunit A | | complement C1q subcomponent subunit B | | complement C1q subcomponent subunit C | | mitogen-activated protein kinase kinase 1 [EC: 2.7.12.2] | | mitogen-activated protein kinase kinase 2 [EC: 2.7.12.2] | | extracellular signal-regulated kinase 1/2 [EC: 2.7.11.24] | | ETS domain-containing protein Elk-1 | | early growth response protein 1 | | C-C motif chemokine 5 | | interleukin 1 alpha | | interleukin 1 beta | | interleukin 6 |
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| Compound |
| Hydrogen peroxide | | 3',5'-Cyclic AMP | | Corticosterone |
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| Reference |
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| Authors |
Kovacs GG, Budka H |
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| Title |
Prion diseases: from protein to cell pathology. |
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| Journal |
Am J Pathol 172:555-65 (2008) |
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| Reference |
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| Authors |
Campana V, Sarnataro D, Zurzolo C |
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| Title |
The highways and byways of prion protein trafficking. |
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| Journal |
Trends Cell Biol 15:102-11 (2005) |
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| Reference |
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| Authors |
Nunziante M, Gilch S, Schatzl HM |
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| Title |
Prion diseases: from molecular biology to intervention strategies. |
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| Journal |
Chembiochem 4:1268-84 (2003) |
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| Reference |
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| Authors |
Caughey B, Baron GS |
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| Title |
Prions and their partners in crime. |
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| Journal |
Nature 443:803-10 (2006) |
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| Reference |
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| Authors |
Linden R, Martins VR, Prado MA, Cammarota M, Izquierdo I, Brentani RR |
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| Title |
Physiology of the prion protein. |
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| Journal |
Physiol Rev 88:673-728 (2008) |
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| Reference |
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| Authors |
Chiesa R, Harris DA |
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| Title |
Prion diseases: what is the neurotoxic molecule? |
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| Journal |
Neurobiol Dis 8:743-63 (2001) |
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| Reference |
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| Authors |
Harris DA |
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| Title |
Cellular biology of prion diseases. |
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| Journal |
Clin Microbiol Rev 12:429-44 (1999) |
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| Reference |
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| Authors |
Marella M, Gaggioli C, Batoz M, Deckert M, Tartare-Deckert S, Chabry J |
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| Title |
Pathological prion protein exposure switches on neuronal mitogen-activated protein kinase pathway resulting in microglia recruitment. |
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| Journal |
J Biol Chem 280:1529-34 (2005) |
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| Reference |
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| Authors |
Mallucci G, Collinge J |
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| Title |
Rational targeting for prion therapeutics. |
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| Journal |
Nat Rev Neurosci 6:23-34 (2005) |
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| Reference |
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| Authors |
Hegde RS, Rane NS |
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| Title |
Prion protein trafficking and the development of neurodegeneration. |
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| Journal |
Trends Neurosci 26:337-9 (2003) |
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| Reference |
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| Authors |
Fasano C, Campana V, Zurzolo C |
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| Title |
Prions: protein only or something more? Overview of potential prion cofactors. |
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| Journal |
J Mol Neurosci 29:195-214 (2006) |
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| Reference |
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| Authors |
Roucou X, Gains M, LeBlanc AC |
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| Title |
Neuroprotective functions of prion protein. |
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| Journal |
J Neurosci Res 75:153-61 (2004) |
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| Reference |
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| Authors |
Novakofski J, Brewer MS, Mateus-Pinilla N, Killefer J, McCusker RH |
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| Title |
Prion biology relevant to bovine spongiform encephalopathy. |
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| Journal |
J Anim Sci 83:1455-76 (2005) |
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| Reference |
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| Authors |
Aguzzi A, Baumann F, Bremer J |
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| Title |
The prion's elusive reason for being. |
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| Journal |
Annu Rev Neurosci 31:439-77 (2008) |
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| Reference |
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| Authors |
Mabbott NA |
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| Title |
The complement system in prion diseases. |
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| Journal |
Curr Opin Immunol 16:587-93 (2004) |
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